chr11-64804766-G-A

Variant names:

• chr11-64804766-G-A
• rs878855190
• NM_001370259.2:c.1401C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001370259.2(MEN1):​c.1401C>T​(p.Ala467Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,596,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A467A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: MEN1 NM_001370259.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -9.22
• Publications: 0 publications found

Genes affected

MEN1 (HGNC:7010): (menin 1) This gene encodes menin, a tumor suppressor associated with a syndrome known as multiple endocrine neoplasia type 1. Menin is a scaffold protein that functions in histone modification and epigenetic gene regulation. It is thought to regulate several pathways and processes by altering chromatin structure through the modification of histones. [provided by RefSeq, May 2019]

MEN1 Gene-Disease associations (from GenCC):

• multiple endocrine neoplasia type 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet, Ambry Genetics
• familial isolated hyperparathyroidism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pituitary gigantism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary pheochromocytoma-paraganglioma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 11-64804766-G-A is Benign according to our data. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-9.22 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEN1	NM_001370259.2	c.1401C>T	p.Ala467Ala	synonymous_variant	Exon 10 of 10	ENST00000450708.7	NP_001357188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEN1	ENST00000450708.7	c.1401C>T	p.Ala467Ala	synonymous_variant	Exon 10 of 10	5	NM_001370259.2	ENSP00000394933.3

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152140 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000222 AC: 5 AN: 224844 AF XY: 0.0000319

Gnomad AFR exome AF: 0.0000736

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000393

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000138 AC: 20 AN: 1444474 Hom.: 0 Cov.: 43 AF XY: 0.0000139 AC XY: 10 AN XY: 718792

African (AFR) AF: 0.0000599 AC: 2 AN: 33416

American (AMR) AF: 0.00 AC: 0 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.00 AC: 0 AN: 86154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5332

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1110806

Other (OTH) AF: 0.0000166 AC: 1 AN: 60084

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152140 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74326

African (AFR) AF: 0.0000483 AC: 2 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000416

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Multiple endocrine neoplasia, type 1 Benign:3

Oct 30, 2023

All of Us Research Program, National Institutes of Health

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 05, 2024

Myriad Genetics, Inc.

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -

not provided Benign:2

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MEN1: BP4, BP7 -

Oct 09, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jun 06, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

MEN1-related disorder Benign:1

Jul 13, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hereditary cancer-predisposing syndrome Benign:1

Oct 16, 2015

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.90
PhyloP100		-9.2
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs878855190; hg19: chr11-64572238;