Variant rs2290647 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PVS1_ModerateBA1

The NM_001320036.2(GRAMD1A):c.1331-2G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,612,494 control chromosomes in the GnomAD database, including 75,002 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7151 hom., cov: 32)

Exomes 𝑓: 0.30 ( 67851 hom. )

Consequence

GRAMD1A
NM_001320036.2 splice_acceptor, intron

Scores

Splicing: ADA: 0.00002610

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.737

Variant links:

Genes affected

GRAMD1A (HGNC:29305): (GRAM domain containing 1A) Predicted to enable cholesterol binding activity and cholesterol transfer activity. Predicted to be involved in cellular response to cholesterol. Located in cytosol; organelle membrane contact site; and plasma membrane. Is extrinsic component of cytoplasmic side of plasma membrane and intrinsic component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

GRAMD1A links:

GRAMD1A (HGNC:):

GRAMD1A links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.057827342 fraction of the gene. Cryptic splice site detected, with MaxEntScore 8.4, offset of 0 (no position change), new splice context is: ctctcctctgtctccagcAGact. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRAMD1A	NM_020895.5 linkuse as main transcript	c.1071G>A	p.Ala357Ala	splice_region_variant, synonymous_variant	11/20	ENST00000317991.10	NP_065946.2	Q96CP6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRAMD1A	ENST00000317991.10 linkuse as main transcript	c.1071G>A	p.Ala357Ala	splice_region_variant, synonymous_variant	11/20	1	NM_020895.5	ENSP00000441032.1		Q96CP6-1

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

46135

AN:

151958

Hom.:

7154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.299

Gnomad ASJ

AF:

0.471

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.327

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.353

GnomAD3 exomes

AF:

0.288

AC:

71233

AN:

247532

Hom.:

10869

AF XY:

0.288

AC XY:

38678

AN XY:

134344

show subpopulations

Gnomad AFR exome

AF:

0.273

Gnomad AMR exome

AF:

0.223

Gnomad ASJ exome

AF:

0.460

Gnomad EAS exome

AF:

0.245

Gnomad SAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.323

Gnomad NFE exome

AF:

0.322

Gnomad OTH exome

AF:

0.332

GnomAD4 exome

AF:

0.300

AC:

438100

AN:

1460418

Hom.:

67851

Cov.:

AF XY:

0.298

AC XY:

216804

AN XY:

726524

show subpopulations

Gnomad4 AFR exome

AF:

0.280

Gnomad4 AMR exome

AF:

0.232

Gnomad4 ASJ exome

AF:

0.463

Gnomad4 EAS exome

AF:

0.241

Gnomad4 SAS exome

AF:

0.184

Gnomad4 FIN exome

AF:

0.316

Gnomad4 NFE exome

AF:

0.308

Gnomad4 OTH exome

AF:

0.315

GnomAD4 genome

AF:

0.303

AC:

46127

AN:

152076

Hom.:

7151

Cov.:

AF XY:

0.302

AC XY:

22463

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.272

Gnomad4 AMR

AF:

0.299

Gnomad4 ASJ

AF:

0.471

Gnomad4 EAS

AF:

0.234

Gnomad4 SAS

AF:

0.178

Gnomad4 FIN

AF:

0.327

Gnomad4 NFE

AF:

0.322

Gnomad4 OTH

AF:

0.351

Alfa

AF:

0.328

Hom.:

18441

Bravo

AF:

0.303

Asia WGS

AF:

0.195

AC:

677

AN:

3478

EpiCase

AF:

0.347

EpiControl

AF:

0.347

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000026

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.99

Position offset: 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

Computational scores

Splicing

Publications

LitVar

Other links and lift over