11-123606644-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

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 (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6062 hom., cov: 32)
  • Exomes 𝑓: 0.32 (75183 hom.)
• Consequence: GRAMD1B NM_001387025.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.755

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]

ACMG classification

Verdict is Benign. Variant got -15 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 criteria_provided_single_submitter, 1 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	UniProt
GRAMD1B	NM_001387025.1	c.1359G>A	p.Glu453=	synonymous_variant	11/20	ENST00000635736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRAMD1B	ENST00000635736.2	c.1359G>A	p.Glu453=	synonymous_variant	11/20	5	NM_001387025.1	P1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42412 AN: 151978 Hom.: 6052 Cov.: 32

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

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.: 36 AF XY: 0.319 AC XY: 231811 AN XY: 725714

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.: 32 AF XY: 0.278 AC XY: 20654 AN XY: 74350

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: criteria provided, single submitter

Submissions by phenotype

GRAMD1B-related disorder Benign:1

Benign, criteria provided, single submitter

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

Other links and lift over

dbSNP: rs2279519; hg19: chr11-123477352; COSMIC: COSV59204454; COSMIC: COSV59204454;