rs4936819

Variant names:

• chr11-123520343-C-A
• rs4936819
• NM_001387025.1:c.452+39450C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387025.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRAMD1B	NM_001387025.1	MANE Select	c.452+39450C>A		intron	N/A	NP_001373954.1
	GRAMD1B	NM_001387024.1		c.452+39450C>A		intron	N/A	NP_001373953.1
	GRAMD1B	NM_001387026.1		c.449+39450C>A		intron	N/A	NP_001373955.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRAMD1B	ENST00000635736.2	TSL:5 MANE Select	c.452+39450C>A		intron	N/A	ENSP00000490062.1
	GRAMD1B	ENST00000638086.1	TSL:5	c.110+28384C>A		intron	N/A	ENSP00000490920.1
	GRAMD1B	ENST00000638157.1	TSL:5	c.-98+39450C>A		intron	N/A	ENSP00000489896.1

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

African (AFR) AF: 0.235 AC: 9733 AN: 41476

American (AMR) AF: 0.0860 AC: 1316 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 234 AN: 3472

East Asian (EAS) AF: 0.0655 AC: 340 AN: 5188

South Asian (SAS) AF: 0.0580 AC: 280 AN: 4826

European-Finnish (FIN) AF: 0.0755 AC: 800 AN: 10598

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0589 AC: 4007 AN: 68004

Other (OTH) AF: 0.0895 AC: 189 AN: 2112

Alfa AF: 0.0945 Hom.: 389

Bravo AF: 0.119

Asia WGS AF: 0.0760 AC: 265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.10
DANN	Benign	0.48
PhyloP100		-0.37

Splicing

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

Other links and lift over

dbSNP: rs4936819; hg19: chr11-123391051;