11-123605469-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001387025.1(GRAMD1B):c.1314C>T(p.Ala438=) 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (16 hom.)
• Consequence: GRAMD1B NM_001387025.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.08

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 -9 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 [Benign]. Clinvar id is 788878.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.08 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRAMD1B	NM_001387025.1	c.1314C>T	p.Ala438=	synonymous_variant	10/20	ENST00000635736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRAMD1B	ENST00000635736.2	c.1314C>T	p.Ala438=	synonymous_variant	10/20	5	NM_001387025.1	P1

Frequencies

GnomAD3 genomes AF: 0.00274 AC: 417 AN: 152128 Hom.: 3 Cov.: 32

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.: 0 AF XY: 0.00250 AC XY: 332 AN XY: 132842

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.: 16 Cov.: 31 AF XY: 0.00361 AC XY: 2618 AN XY: 725146

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.: 3 Cov.: 32 AF XY: 0.00274 AC XY: 204 AN XY: 74452

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.: 0

Bravo AF: 0.00267

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00402

EpiControl AF: 0.00403

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 05, 2018

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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

Other links and lift over

dbSNP: rs75493628; hg19: chr11-123476177;