11-123598257-A-G

Variant names:

• chr11-123598257-A-G
• rs1709905
• NM_001387025.1:c.970-2211A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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:23277): (splicing factor 3a, subunit 3 pseudogene 2)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GRAMD1B	NM_001387025.1	c.970-2211A>G		intron_variant	Intron 7 of 19	ENST00000635736.2	NP_001373954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRAMD1B	ENST00000635736.2	c.970-2211A>G		intron_variant	Intron 7 of 19	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

African (AFR) AF: 0.760 AC: 21899 AN: 28832

American (AMR) AF: 0.870 AC: 38537 AN: 44316

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 20862 AN: 24682

East Asian (EAS) AF: 0.993 AC: 38264 AN: 38534

South Asian (SAS) AF: 0.915 AC: 74241 AN: 81156

European-Finnish (FIN) AF: 0.803 AC: 42683 AN: 53128

Middle Eastern (MID) AF: 0.731 AC: 2713 AN: 3712

European-Non Finnish (NFE) AF: 0.835 AC: 750737 AN: 899406

Other (OTH) AF: 0.842 AC: 44048 AN: 52284

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

African (AFR) AF: 0.768 AC: 31803 AN: 41386

American (AMR) AF: 0.841 AC: 12853 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2940 AN: 3468

East Asian (EAS) AF: 0.993 AC: 5121 AN: 5156

South Asian (SAS) AF: 0.917 AC: 4413 AN: 4810

European-Finnish (FIN) AF: 0.780 AC: 8182 AN: 10486

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.834 AC: 56653 AN: 67918

Other (OTH) AF: 0.809 AC: 1702 AN: 2104

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
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1709905; hg19: chr11-123468965;