rs4936819

Positions:

• chr11-123520343-C-A

Variant summary

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

The NM_001387025.1(GRAMD1B):​c.452+39450C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,178 control chromosomes in the GnomAD database, including 1,455 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 0.11 (1455 hom., cov: 32)
• Consequence: GRAMD1B NM_001387025.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRAMD1B	NM_001387025.1	c.452+39450C>A		intron_variant		ENST00000635736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRAMD1B	ENST00000635736.2	c.452+39450C>A		intron_variant		5	NM_001387025.1	P1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16990 AN: 152058 Hom.: 1452 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.0656

Gnomad SAS AF: 0.0582

Gnomad FIN AF: 0.0755

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0589

Gnomad OTH AF: 0.0905

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.112 AC: 17013 AN: 152178 Hom.: 1455 Cov.: 32 AF XY: 0.110 AC XY: 8183 AN XY: 74394

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.0860

Gnomad4 ASJ AF: 0.0674

Gnomad4 EAS AF: 0.0655

Gnomad4 SAS AF: 0.0580

Gnomad4 FIN AF: 0.0755

Gnomad4 NFE AF: 0.0589

Gnomad4 OTH AF: 0.0895

Alfa AF: 0.0943 Hom.: 320

Bravo AF: 0.119

Asia WGS AF: 0.0760 AC: 265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.10
DANN	Benign	0.48

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4936819; hg19: chr11-123391051;