Variant 11-123605469-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001387025.1(GRAMD1B):c.1314C>T(p.Ala438Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00362 in 1,609,956 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 16 hom. )

Consequence

GRAMD1B
NM_001387025.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.08

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 11-123605469-C-T is Benign according to our data. Variant chr11-123605469-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 788878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.08 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRAMD1B	NM_001387025.1 link	c.1314C>T	p.Ala438Ala	synonymous_variant	10/20	ENST00000635736.2	NP_001373954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRAMD1B	ENST00000635736.2 link	c.1314C>T	p.Ala438Ala	synonymous_variant	10/20	5	NM_001387025.1	ENSP00000490062.1		A0A1B0GUD6

Frequencies

GnomAD3 genomes

AF:

0.00274

AC:

417

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00432

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00230

AC:

562

AN:

244764

Hom.:

AF XY:

0.00250

AC XY:

332

AN XY:

132842

show subpopulations

Gnomad AFR exome

AF:

0.000785

Gnomad AMR exome

AF:

0.00125

Gnomad ASJ exome

AF:

0.000204

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00230

Gnomad FIN exome

AF:

0.000467

Gnomad NFE exome

AF:

0.00375

Gnomad OTH exome

AF:

0.00170

GnomAD4 exome

AF:

0.00371

AC:

5411

AN:

1457710

Hom.:

Cov.:

AF XY:

0.00361

AC XY:

2618

AN XY:

725146

show subpopulations

Gnomad4 AFR exome

AF:

0.000420

Gnomad4 AMR exome

AF:

0.00115

Gnomad4 ASJ exome

AF:

0.000193

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00217

Gnomad4 FIN exome

AF:

0.000488

Gnomad4 NFE exome

AF:

0.00441

Gnomad4 OTH exome

AF:

0.00389

GnomAD4 genome

AF:

0.00274

AC:

417

AN:

152246

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

204

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00432

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00320

Hom.:

Bravo

AF:

0.00267

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00402

EpiControl

AF:

0.00403

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	GRAMD1B: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

5.7

DANN

Benign

0.72

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