12-103593967-A-G

Position:

• chr12-103593967-A-G

Variant summary

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

The ENST00000388887.7(STAB2):​c.216-428A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 152,262 control chromosomes in the GnomAD database, including 177 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 0.040 (177 hom., cov: 32)
• Consequence: STAB2 ENST00000388887.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAB2	NM_017564.10	c.216-428A>G		intron_variant		ENST00000388887.7	NP_060034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAB2	ENST00000388887.7	c.216-428A>G		intron_variant		1	NM_017564.10	ENSP00000373539	P1

Frequencies

GnomAD3 genomes AF: 0.0398 AC: 6054 AN: 152142 Hom.: 176 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.0516

Gnomad ASJ AF: 0.0482

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0715

Gnomad FIN AF: 0.0504

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0493

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

GnomAD4 genome AF: 0.0397 AC: 6052 AN: 152262 Hom.: 177 Cov.: 32 AF XY: 0.0411 AC XY: 3062 AN XY: 74444

Gnomad4 AFR AF: 0.0109

Gnomad4 AMR AF: 0.0516

Gnomad4 ASJ AF: 0.0482

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.0716

Gnomad4 FIN AF: 0.0504

Gnomad4 NFE AF: 0.0442

Gnomad4 OTH AF: 0.0493

Alfa AF: 0.0375 Hom.: 62

Bravo AF: 0.0379

Asia WGS AF: 0.0870 AC: 305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.53

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: rs10507167; hg19: chr12-103987745;