rs12229292

Variant names:

• chr12-103759855-G-T
• rs12229292
• NM_017564.10:c.7248+582G>T

Variant summary

Our verdict is Benign. Variant got -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

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:):

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAB2	NM_017564.10	c.7248+582G>T		intron_variant	Intron 65 of 68	ENST00000388887.7	NP_060034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAB2	ENST00000388887.7	c.7248+582G>T		intron_variant	Intron 65 of 68	1	NM_017564.10	ENSP00000373539.2
STAB2	ENST00000548579.1	n.506+582G>T		intron_variant	Intron 2 of 2	4
ENSG00000257681	ENST00000551299.1	n.172+6880C>A		intron_variant	Intron 1 of 1	3

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

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.251

Alfa AF: 0.257 Hom.: 4733

Bravo AF: 0.232

Asia WGS AF: 0.429 AC: 1491 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	1.1
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs12229292; hg19: chr12-104153633;