rs11219172

Variant names:

• chr11-123499752-C-A
• rs11219172
• NM_001387025.1:c.452+18859C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-123499752-C-A
• chr11-123499752-C-T

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+18859C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0928 in 152,132 control chromosomes in the GnomAD database, including 906 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 0.093 (906 hom., cov: 33)
• Consequence: GRAMD1B NM_001387025.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRAMD1B	NM_001387025.1	c.452+18859C>A		intron_variant	Intron 2 of 19	ENST00000635736.2	NP_001373954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRAMD1B	ENST00000635736.2	c.452+18859C>A		intron_variant	Intron 2 of 19	5	NM_001387025.1	ENSP00000490062.1

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 14115 AN: 152012 Hom.: 910 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0736

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.0380

Gnomad SAS AF: 0.0571

Gnomad FIN AF: 0.0754

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0577

Gnomad OTH AF: 0.0762

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

GnomAD4 genome AF: 0.0928 AC: 14121 AN: 152132 Hom.: 906 Cov.: 33 AF XY: 0.0925 AC XY: 6878 AN XY: 74366

African (AFR) AF: 0.180 AC: 7484 AN: 41478

American (AMR) AF: 0.0735 AC: 1123 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3470

East Asian (EAS) AF: 0.0380 AC: 197 AN: 5178

South Asian (SAS) AF: 0.0563 AC: 271 AN: 4812

European-Finnish (FIN) AF: 0.0754 AC: 798 AN: 10578

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0577 AC: 3923 AN: 68014

Other (OTH) AF: 0.0754 AC: 159 AN: 2108

Alfa AF: 0.0829 Hom.: 124

Bravo AF: 0.0967

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.36
DANN	Benign	0.47
PhyloP100		-0.40

Splicing

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

Other links and lift over

dbSNP: rs11219172; hg19: chr11-123370460;