rs4981022

Variant names:

• chr12-103756096-G-A
• rs4981022
• NM_017564.10:c.6987+378G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-103756096-G-A
• chr12-103756096-G-C
• chr12-103756096-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017564.10(STAB2):​c.6987+378G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 149,740 control chromosomes in the GnomAD database, including 35,776 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 0.69 (35776 hom., cov: 30)
• Consequence: STAB2 NM_017564.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 18 publications found

Genes affected

STAB2 (HGNC:18629): (stabilin 2) This gene encodes a large, transmembrane receptor protein which may function in angiogenesis, lymphocyte homing, cell adhesion, or receptor scavenging. The protein contains 7 fasciclin, 15 epidermal growth factor (EGF)-like, and 2 laminin-type EGF-like domains as well as a C-type lectin-like hyaluronan-binding Link module. The protein is primarily expressed on sinusoidal endothelial cells of liver, spleen, and lymph node. The receptor has been shown to bind and endocytose ligands such as hyaluronan, low density lipoprotein, Gram-positive and Gram-negative bacteria, and advanced glycosylation end products. Supporting its possible role as a scavenger receptor, the protein has been shown to cycle between the plasma membrane and lysosomes. [provided by RefSeq, Jul 2008]

ENSG00000257681 (HGNC:58447):

NT5DC3 (HGNC:30826): (5'-nucleotidase domain containing 3) Predicted to enable 5'-nucleotidase activity. Predicted to be involved in dephosphorylation. Part of receptor complex. [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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAB2	NM_017564.10	c.6987+378G>A		intron_variant	Intron 63 of 68	ENST00000388887.7	NP_060034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAB2	ENST00000388887.7	c.6987+378G>A		intron_variant	Intron 63 of 68	1	NM_017564.10	ENSP00000373539.2
STAB2	ENST00000548073.1	n.483+378G>A		intron_variant	Intron 2 of 2	5
ENSG00000257681	ENST00000551299.1	n.173-9457C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.693 AC: 103733 AN: 149622 Hom.: 35735 Cov.: 30

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.735

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.693 AC: 103826 AN: 149740 Hom.: 35776 Cov.: 30 AF XY: 0.700 AC XY: 51285 AN XY: 73314

African (AFR) AF: 0.684 AC: 27984 AN: 40894

American (AMR) AF: 0.771 AC: 11607 AN: 15048

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2356 AN: 3412

East Asian (EAS) AF: 0.760 AC: 3854 AN: 5070

South Asian (SAS) AF: 0.802 AC: 3817 AN: 4758

European-Finnish (FIN) AF: 0.688 AC: 7222 AN: 10492

Middle Eastern (MID) AF: 0.733 AC: 211 AN: 288

European-Non Finnish (NFE) AF: 0.669 AC: 44712 AN: 66788

Other (OTH) AF: 0.699 AC: 1460 AN: 2088

Alfa AF: 0.695 Hom.: 60541

Bravo AF: 0.708

Asia WGS AF: 0.782 AC: 2719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.22
PhyloP100		0.0
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: rs4981022; hg19: chr12-104149874;