11-123598257-A-G

Position:

• chr11-123598257-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387025.1(GRAMD1B):​c.970-2211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 151,800 control chromosomes in the GnomAD database, including 51,365 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.82 (51365 hom., cov: 32)
  • Exomes 𝑓: 0.84 (437418 hom.)
  • Failed GnomAD Quality Control
• Consequence: GRAMD1B NM_001387025.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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]

SF3A3P2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRAMD1B	NM_001387025.1	c.970-2211A>G		intron_variant		ENST00000635736.2	NP_001373954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRAMD1B	ENST00000635736.2	c.970-2211A>G		intron_variant		5	NM_001387025.1	ENSP00000490062.1

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124501 AN: 151682 Hom.: 51333 Cov.: 32

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.807

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.843 AC: 1033984 AN: 1226050 Hom.: 437418 Cov.: 24 AF XY: 0.846 AC XY: 525143 AN XY: 621008

Gnomad4 AFR exome AF: 0.760

Gnomad4 AMR exome AF: 0.870

Gnomad4 ASJ exome AF: 0.845

Gnomad4 EAS exome AF: 0.993

Gnomad4 SAS exome AF: 0.915

Gnomad4 FIN exome AF: 0.803

Gnomad4 NFE exome AF: 0.835

Gnomad4 OTH exome AF: 0.842

GnomAD4 genome AF: 0.821 AC: 124585 AN: 151800 Hom.: 51365 Cov.: 32 AF XY: 0.821 AC XY: 60863 AN XY: 74120

Gnomad4 AFR AF: 0.768

Gnomad4 AMR AF: 0.841

Gnomad4 ASJ AF: 0.848

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.917

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.834

Gnomad4 OTH AF: 0.809

Alfa AF: 0.826 Hom.: 6065

Bravo AF: 0.822

Asia WGS AF: 0.937 AC: 3261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.4
DANN	Benign	0.59

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: rs1709905; hg19: chr11-123468965;