rs12229292

Variant names:

• chr12-103759855-G-T
• rs12229292
• NM_017564.10:c.7248+582G>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.7248+582G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,162 control chromosomes in the GnomAD database, including 4,625 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 0.23 (4625 hom., cov: 33)
• Consequence: STAB2 NM_017564.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.419 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.7248+582G>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.7248+582G>T		intron	N/A	ENSP00000373539.2	Q8WWQ8
	STAB2	ENST00000548579.1	TSL:4	n.506+582G>T		intron	N/A
	ENSG00000257681	ENST00000551299.1	TSL:3	n.172+6880C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35533 AN: 152044 Hom.: 4620 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.234 AC: 35546 AN: 152162 Hom.: 4625 Cov.: 33 AF XY: 0.238 AC XY: 17708 AN XY: 74404

African (AFR) AF: 0.139 AC: 5779 AN: 41520

American (AMR) AF: 0.268 AC: 4093 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1020 AN: 3470

East Asian (EAS) AF: 0.433 AC: 2240 AN: 5174

South Asian (SAS) AF: 0.434 AC: 2094 AN: 4824

European-Finnish (FIN) AF: 0.202 AC: 2142 AN: 10586

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17346 AN: 67996

Other (OTH) AF: 0.251 AC: 528 AN: 2106

Alfa AF: 0.253 Hom.: 6111

Bravo AF: 0.232

Asia WGS AF: 0.429 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.74
PhyloP100		-0.072
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: rs12229292; hg19: chr12-104153633;