11-64804766-G-C

Variant names:

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

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>G​(p.Ala467Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000485 in 1,444,474 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: MEN1 NM_001370259.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• 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=-1.03).
• BP6: Variant 11-64804766-G-C is Benign according to our data. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64804766-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 2560722.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 7 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000485 AC: 7 AN: 1444474 Hom.: 0 Cov.: 43 AF XY: 0.00000556 AC XY: 4 AN XY: 718792

African (AFR) AF: 0.00 AC: 0 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: 0.0000116 AC: 1 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: 0.00000540 AC: 6 AN: 1110806

Other (OTH) AF: 0.00 AC: 0 AN: 60084

GnomAD4 genome Cov.: 33

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Multiple endocrine neoplasia, type 1 Benign:3

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. -

Jan 14, 2024

Color Diagnostics, LLC DBA Color Health

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Nov 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MEN1: PM2:Supporting, BP4, BP7 -

Hereditary cancer-predisposing syndrome Benign:1

May 19, 2023

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	0.064
DANN	Benign	0.80
PhyloP100		-9.2

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;