rs4981021

Variant names:

• chr12-103756221-C-T
• rs4981021
• NM_017564.10:c.6987+503C>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+503C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,100 control chromosomes in the GnomAD database, including 5,103 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 0.24 (5103 hom., cov: 33)
• Consequence: STAB2 NM_017564.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.986
• Publications: 11 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017564.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAB2	NM_017564.10	MANE Select	c.6987+503C>T		intron	N/A	NP_060034.9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAB2	ENST00000388887.7	TSL:1 MANE Select	c.6987+503C>T		intron	N/A	ENSP00000373539.2	Q8WWQ8
	STAB2	ENST00000548073.1	TSL:5	n.483+503C>T		intron	N/A
	ENSG00000257681	ENST00000551299.1	TSL:3	n.173-9582G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37208 AN: 151982 Hom.: 5097 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.245 AC: 37225 AN: 152100 Hom.: 5103 Cov.: 33 AF XY: 0.250 AC XY: 18579 AN XY: 74352

African (AFR) AF: 0.137 AC: 5680 AN: 41482

American (AMR) AF: 0.271 AC: 4146 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1044 AN: 3472

East Asian (EAS) AF: 0.483 AC: 2495 AN: 5170

South Asian (SAS) AF: 0.425 AC: 2051 AN: 4828

European-Finnish (FIN) AF: 0.255 AC: 2699 AN: 10572

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18217 AN: 67982

Other (OTH) AF: 0.264 AC: 556 AN: 2110

Alfa AF: 0.267 Hom.: 23847

Bravo AF: 0.240

Asia WGS AF: 0.446 AC: 1550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.59
PhyloP100		-0.99
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: rs4981021; hg19: chr12-104149999;