Variant 11-123605400-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001387025.1(GRAMD1B):c.1245T>A(p.Asp415Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00073 in 1,613,430 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 4 hom. )

Consequence

GRAMD1B
NM_001387025.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.414

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047641993).

BP6

Variant 11-123605400-T-A is Benign according to our data. Variant chr11-123605400-T-A is described in ClinVar as [Benign]. Clinvar id is 791359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRAMD1B	NM_001387025.1 linkuse as main transcript	c.1245T>A	p.Asp415Glu	missense_variant	10/20	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.1245T>A	p.Asp415Glu	missense_variant	10/20	5	NM_001387025.1	ENSP00000490062	P1

Frequencies

GnomAD3 genomes

AF:

0.00391

AC:

594

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

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:

0.0000735

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00101

AC:

252

AN:

248898

Hom.:

AF XY:

0.000770

AC XY:

104

AN XY:

135012

show subpopulations

Gnomad AFR exome

AF:

0.0131

Gnomad AMR exome

AF:

0.00105

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:

0.0000620

Gnomad OTH exome

AF:

0.000996

GnomAD4 exome

AF:

0.000396

AC:

578

AN:

1461232

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

274

AN XY:

726892

show subpopulations

Gnomad4 AFR exome

AF:

0.0130

Gnomad4 AMR exome

AF:

0.00125

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:

0.0000189

Gnomad4 OTH exome

AF:

0.000994

GnomAD4 genome

AF:

0.00394

AC:

599

AN:

152198

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

291

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0130

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000535

Hom.:

Bravo

AF:

0.00456

ESP6500AA

AF:

0.0127

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00116

AC:

141

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000238

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 08, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.3

DANN

Benign

0.49

DEOGEN2

Benign

0.0028

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

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.38

LIST_S2

Uncertain

0.88

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

MetaRNN

Benign

0.0048

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

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.86

D;D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

1.1

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

REVEL

Benign

0.21

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

Polyphen

0.0

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

Vest4

0.056, 0.054, 0.034, 0.049

MutPred

0.12

.;.;.;Gain of methylation at K277 (P = 0.1556);.;.;.;.;.;

MVP

0.043

MPC

0.34

ClinPred

0.0056

GERP RS

2.7

Varity_R

0.041

gMVP

0.14

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