Variant 11-123606644-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001387025.1(GRAMD1B):c.1359G>A(p.Glu453=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,611,422 control chromosomes in the GnomAD database, including 81,245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.28 ( 6062 hom., cov: 32)

Exomes 𝑓: 0.32 ( 75183 hom. )

Consequence

GRAMD1B
NM_001387025.1 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.755

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 11-123606644-G-A is Benign according to our data. Variant chr11-123606644-G-A is described in ClinVar as [Benign]. Clinvar id is 3061028.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.755 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRAMD1B	NM_001387025.1 linkuse as main transcript	c.1359G>A	p.Glu453=	synonymous_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.1359G>A	p.Glu453=	synonymous_variant	11/20	5	NM_001387025.1	ENSP00000490062	P1

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

42412

AN:

151978

Hom.:

6052

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.252

Gnomad ASJ

AF:

0.282

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.410

Gnomad FIN

AF:

0.269

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.246

GnomAD3 exomes

AF:

0.300

AC:

73615

AN:

245384

Hom.:

11557

AF XY:

0.305

AC XY:

40563

AN XY:

133052

show subpopulations

Gnomad AFR exome

AF:

0.223

Gnomad AMR exome

AF:

0.287

Gnomad ASJ exome

AF:

0.278

Gnomad EAS exome

AF:

0.161

Gnomad SAS exome

AF:

0.404

Gnomad FIN exome

AF:

0.281

Gnomad NFE exome

AF:

0.316

Gnomad OTH exome

AF:

0.274

GnomAD4 exome

AF:

0.317

AC:

462774

AN:

1459326

Hom.:

75183

Cov.:

AF XY:

0.319

AC XY:

231811

AN XY:

725714

show subpopulations

Gnomad4 AFR exome

AF:

0.224

Gnomad4 AMR exome

AF:

0.282

Gnomad4 ASJ exome

AF:

0.279

Gnomad4 EAS exome

AF:

0.233

Gnomad4 SAS exome

AF:

0.400

Gnomad4 FIN exome

AF:

0.285

Gnomad4 NFE exome

AF:

0.321

Gnomad4 OTH exome

AF:

0.307

GnomAD4 genome

AF:

0.279

AC:

42462

AN:

152096

Hom.:

6062

Cov.:

AF XY:

0.278

AC XY:

20654

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.226

Gnomad4 AMR

AF:

0.252

Gnomad4 ASJ

AF:

0.282

Gnomad4 EAS

AF:

0.184

Gnomad4 SAS

AF:

0.411

Gnomad4 FIN

AF:

0.269

Gnomad4 NFE

AF:

0.318

Gnomad4 OTH

AF:

0.253

Alfa

AF:

0.302

Hom.:

16731

Bravo

AF:

0.273

Asia WGS

AF:

0.328

AC:

1137

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GRAMD1B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as 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

BayesDel_noAF

Benign

-0.50

CADD

Benign

5.0

DANN

Benign

0.53

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