rs4981021

Positions:

• chr12-103756221-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.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

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]

STAB2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAB2	NM_017564.10	c.6987+503C>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.6987+503C>T		intron_variant		1	NM_017564.10	ENSP00000373539.2
STAB2	ENST00000548073.1	n.483+503C>T		intron_variant		5
ENSG00000257681	ENST00000551299.1	n.173-9582G>A		intron_variant		3

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

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.264

Alfa AF: 0.273 Hom.: 11996

Bravo AF: 0.240

Asia WGS AF: 0.446 AC: 1550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.59

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: rs4981021; hg19: chr12-104149999;