12-103654676-C-A

Variant names:

• chr12-103654676-C-A
• rs1609860
• NM_017564.10:c.1529C>A

Variant summary

Our verdict is Benign. The variant received -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 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
• Publications: 26 publications found

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]

ENSG00000257737 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017564.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAB2	NM_017564.10	MANE Select	c.1529C>A	p.Pro510His	missense	Exon 13 of 69	NP_060034.9

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAB2	ENST00000388887.7	TSL:1 MANE Select	c.1529C>A	p.Pro510His	missense	Exon 13 of 69	ENSP00000373539.2
	ENSG00000257737	ENST00000551905.1	TSL:3	n.*104G>T		downstream_gene	N/A

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

GnomAD2 exomes AF: 0.102 AC: 25516 AN: 251072 AF XY: 0.106

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 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

African (AFR) AF: 0.0127 AC: 425 AN: 33464

American (AMR) AF: 0.102 AC: 4552 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.0807 AC: 2107 AN: 26118

East Asian (EAS) AF: 0.138 AC: 5459 AN: 39690

South Asian (SAS) AF: 0.163 AC: 14030 AN: 86174

European-Finnish (FIN) AF: 0.171 AC: 9129 AN: 53416

Middle Eastern (MID) AF: 0.121 AC: 696 AN: 5768

European-Non Finnish (NFE) AF: 0.0822 AC: 91346 AN: 1111864

Other (OTH) AF: 0.101 AC: 6118 AN: 60372

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

African (AFR) AF: 0.0151 AC: 626 AN: 41544

American (AMR) AF: 0.103 AC: 1573 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3470

East Asian (EAS) AF: 0.114 AC: 593 AN: 5182

South Asian (SAS) AF: 0.160 AC: 772 AN: 4820

European-Finnish (FIN) AF: 0.184 AC: 1951 AN: 10600

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0858 AC: 5838 AN: 68022

Other (OTH) AF: 0.0979 AC: 207 AN: 2114

Alfa AF: 0.0810 Hom.: 1769

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 v4.9

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
PhyloP100		6.4
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
Mutation Taster		=86/14	polymorphism (auto)

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

Other links and lift over

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