Variant 11-64805085-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001370259.2(MEN1):c.1299T>C(p.His433=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,614,144 control chromosomes in the GnomAD database, including 800,746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.98 ( 72937 hom., cov: 36)

Exomes 𝑓: 1.0 ( 727809 hom. )

Consequence

MEN1
NM_001370259.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.301

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 11-64805085-A-G is Benign according to our data. Variant chr11-64805085-A-G is described in ClinVar as [Benign]. Clinvar id is 167288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805085-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.301 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEN1	NM_001370259.2 linkuse as main transcript	c.1299T>C	p.His433=	synonymous_variant	9/10	ENST00000450708.7	NP_001357188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEN1	ENST00000450708.7 linkuse as main transcript	c.1299T>C	p.His433=	synonymous_variant	9/10	5	NM_001370259.2	ENSP00000394933	P3	O00255-2

Frequencies

GnomAD3 genomes

AF:

0.978

AC:

148864

AN:

152214

Hom.:

72884

Cov.:

show subpopulations

Gnomad AFR

AF:

0.923

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.993

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.984

GnomAD3 exomes

AF:

0.994

AC:

249724

AN:

251190

Hom.:

124180

AF XY:

0.996

AC XY:

135273

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.919

Gnomad AMR exome

AF:

0.997

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.996

GnomAD4 exome

AF:

0.998

AC:

1458581

AN:

1461812

Hom.:

727809

Cov.:

AF XY:

0.998

AC XY:

725854

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.919

Gnomad4 AMR exome

AF:

0.997

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.995

GnomAD4 genome

AF:

0.978

AC:

148976

AN:

152332

Hom.:

72937

Cov.:

AF XY:

0.978

AC XY:

72873

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.923

Gnomad4 AMR

AF:

0.993

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.984

Alfa

AF:

0.991

Hom.:

34255

Bravo

AF:

0.975

Asia WGS

AF:

0.995

AC:

3461

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

1.00

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 23, 2016	c.1314T>C in exon 10 of MEN1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 99.99% (66603/66608) o f European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs540012). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 22, 2018	- -

Multiple endocrine neoplasia, type 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Mar 29, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.0

DANN

Benign

0.54

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over