12-103640541-C-T

Position:

• chr12-103640541-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017564.10(STAB2):​c.1040+285C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,894 control chromosomes in the GnomAD database, including 16,626 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 0.46 (16626 hom., cov: 32)
• Consequence: STAB2 NM_017564.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAB2	NM_017564.10	c.1040+285C>T		intron_variant		ENST00000388887.7	NP_060034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAB2	ENST00000388887.7	c.1040+285C>T		intron_variant		1	NM_017564.10	ENSP00000373539.2

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69601 AN: 151776 Hom.: 16620 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.458 AC: 69616 AN: 151894 Hom.: 16626 Cov.: 32 AF XY: 0.453 AC XY: 33654 AN XY: 74236

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.445

Alfa AF: 0.394 Hom.: 3571

Bravo AF: 0.451

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.73

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: rs1650123; hg19: chr12-104034319; COSMIC: COSV66348106;