Variant 11-123606682-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_001387025.1(GRAMD1B):c.1397A>G(p.Asn466Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000279 in 1,613,520 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

GRAMD1B
NM_001387025.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.344

Variant links:

Genes affected

GRAMD1B (HGNC:29214): (GRAM domain containing 1B) Predicted to enable cholesterol binding activity; cholesterol transfer activity; and phospholipid binding activity. Predicted to be involved in cellular response to cholesterol and cholesterol homeostasis. Located in endoplasmic reticulum membrane; endoplasmic reticulum-plasma membrane contact site; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

GRAMD1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.004298866).

BP6

Variant 11-123606682-A-G is Benign according to our data. Variant chr11-123606682-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3042797.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRAMD1B	NM_001387025.1 linkuse as main transcript	c.1397A>G	p.Asn466Ser	missense_variant	11/20	ENST00000635736.2	NP_001373954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRAMD1B	ENST00000635736.2 linkuse as main transcript	c.1397A>G	p.Asn466Ser	missense_variant	11/20	5	NM_001387025.1	ENSP00000490062	P1

Frequencies

GnomAD3 genomes

AF:

0.00167

AC:

254

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00584

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.0000147

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000431

AC:

107

AN:

248386

Hom.:

AF XY:

0.000334

AC XY:

AN XY:

134716

show subpopulations

Gnomad AFR exome

AF:

0.00616

Gnomad AMR exome

AF:

0.000320

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000134

AC:

196

AN:

1461274

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.00490

Gnomad4 AMR exome

AF:

0.000336

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.00167

AC:

254

AN:

152246

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00582

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000268

Hom.:

Bravo

AF:

0.00178

ESP6500AA

AF:

0.00530

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000521

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GRAMD1B-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 24, 2019

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.1

DANN

Benign

0.58

DEOGEN2

Benign

0.0022

T;T;T;.;T;T;.;.;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.55

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.90

D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.0043

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

0.71

D;D;D;D

PrimateAI

Benign

0.33

PROVEAN

Benign

0.32

.;.;.;N;N;N;N;N;.

REVEL

Benign

0.036

Sift

Benign

0.76

.;.;.;T;T;T;T;T;.

Sift4G

Benign

0.74

.;.;.;T;T;T;T;T;.

Polyphen

0.0

.;.;.;.;.;B;.;.;.

Vest4

0.057, 0.091, 0.071, 0.073

MVP

0.043

MPC

0.29

ClinPred

0.0022

GERP RS

0.31

Varity_R

0.018

gMVP

0.13

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