Variant 11-123606675-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001387025.1(GRAMD1B):c.1390A>G(p.Ile464Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,613,494 control chromosomes in the GnomAD database, including 20 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 (★).

Frequency

Genomes: 𝑓 0.00088 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 18 hom. )

Consequence

GRAMD1B
NM_001387025.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.54

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:

GRAMD1B (HGNC:):

GRAMD1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061227083).

BP6

Variant 11-123606675-A-G is Benign according to our data. Variant chr11-123606675-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2642483.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRAMD1B	NM_001387025.1 linkuse as main transcript	c.1390A>G	p.Ile464Val	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.1390A>G	p.Ile464Val	missense_variant	11/20	5	NM_001387025.1	ENSP00000490062.1		A0A1B0GUD6

Frequencies

GnomAD3 genomes

AF:

0.000887

AC:

135

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00177

AC:

439

AN:

248212

Hom.:

AF XY:

0.00198

AC XY:

267

AN XY:

134630

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.0176

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00505

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000719

Gnomad OTH exome

AF:

0.00348

GnomAD4 exome

AF:

0.00105

AC:

1533

AN:

1461204

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

921

AN XY:

726800

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.0186

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00522

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000324

Gnomad4 OTH exome

AF:

0.00250

GnomAD4 genome

AF:

0.000880

AC:

134

AN:

152290

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00602

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00140

Hom.:

Bravo

AF:

0.000744

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000843

AC:

ExAC

AF:

0.00174

AC:

210

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000981

EpiControl

AF:

0.00190

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

GRAMD1B: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0018

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

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.86

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

M_CAP

Benign

0.0096

MetaRNN

Benign

0.0061

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

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

0.080

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

REVEL

Benign

0.021

Sift

Benign

0.61

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

Sift4G

Benign

0.59

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

Polyphen

0.0

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

Vest4

0.10, 0.12, 0.12, 0.11

MVP

0.043

MPC

0.31

ClinPred

0.025

GERP RS

2.7

Varity_R

0.025

gMVP

0.17

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