rs1609860

chr12-103654676-C-Achr12-103654676-C-G

Variant summary

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

The NM_017564.10(STAB2):c.1529C>A(p.Pro510His) variant causes a missense change. The variant allele was found at a frequency of 0.0903 in 1,613,778 control chromosomes in the GnomAD database, including 7,556 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P510R) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.078 (636 hom., cov: 32)
  • Exomes 𝑓: 0.092 (6920 hom.)
• Consequence: STAB2 NM_017564.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.41

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 (MetaRNN=0.0023873448).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAB2	NM_017564.10	c.1529C>A	p.Pro510His	missense_variant	13/69	ENST00000388887.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAB2	ENST00000388887.7	c.1529C>A	p.Pro510His	missense_variant	13/69	1	NM_017564.10	P1

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11884 AN: 152124 Hom.: 634 Cov.: 32

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.0946

GnomAD3 exomes AF: 0.102 AC: 25516 AN: 251072 Hom.: 1528 AF XY: 0.106 AC XY: 14372 AN XY: 135698

Gnomad AFR exome AF: 0.0134

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.0806

Gnomad EAS exome AF: 0.106

Gnomad SAS exome AF: 0.160

Gnomad FIN exome AF: 0.175

Gnomad NFE exome AF: 0.0852

Gnomad OTH exome AF: 0.101

GnomAD4 exome AF: 0.0916 AC: 133862 AN: 1461536 Hom.: 6920 Cov.: 31 AF XY: 0.0943 AC XY: 68575 AN XY: 727054

Gnomad4 AFR exome AF: 0.0127

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.0807

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.171

Gnomad4 NFE exome AF: 0.0822

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.0781 AC: 11884 AN: 152242 Hom.: 636 Cov.: 32 AF XY: 0.0848 AC XY: 6316 AN XY: 74444

Gnomad4 AFR AF: 0.0151

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0804

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.0858

Gnomad4 OTH AF: 0.0979

Alfa AF: 0.0832 Hom.: 1209

Bravo AF: 0.0665

TwinsUK AF: 0.0809 AC: 300

ALSPAC AF: 0.0789 AC: 304

ESP6500AA AF: 0.0172 AC: 76

ESP6500EA AF: 0.0807 AC: 694

ExAC AF: 0.100 AC: 12155

EpiCase AF: 0.0879

EpiControl AF: 0.0887

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.25
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	3.4	M
MutationTaster	Benign	0.00076	P
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.33
MPC		0.47
ClinPred		0.031	T
GERP RS		5.8
Varity_R		0.57
gMVP		0.65

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: rs1609860; hg19: chr12-104048454; COSMIC: COSV66347810; COSMIC: COSV66347810;