Genetic Variant STAB1:p.Arg61Pro (chr3-52501269-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_015136.3(STAB1):c.182G>C(p.Arg61Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. R61Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

STAB1
NM_015136.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0940

Publications

1 publications found

Variant links:

Genes affected

STAB1 (HGNC:18628): (stabilin 1) 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, 16 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 endocytose ligands such as low density lipoprotein, Gram-positive and Gram-negative bacteria, and advanced glycosylation end products. Supporting its possible role as a scavenger receptor, the protein rapidly cycles between the plasma membrane and early endosomes. [provided by RefSeq, Jul 2008]

STAB1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26626736).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015136.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAB1	NM_015136.3	MANE Select	c.182G>C	p.Arg61Pro	missense	Exon 2 of 69	NP_055951.2	Q9NY15-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STAB1	ENST00000321725.10	TSL:1 MANE Select	c.182G>C	p.Arg61Pro	missense	Exon 2 of 69	ENSP00000312946.6	Q9NY15-1
STAB1	ENST00000481607.1	TSL:1	n.237G>C		non_coding_transcript_exon	Exon 2 of 21
STAB1	ENST00000899926.1		c.182G>C	p.Arg61Pro	missense	Exon 2 of 69	ENSP00000569985.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251072

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152372

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41596

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.35

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.62

M_CAP

Benign

0.0056

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.69

PhyloP100

-0.094

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.16

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0050

Polyphen

0.95

Vest4

0.41

MVP

0.45

MPC

0.29

ClinPred

0.37

GERP RS

-1.1

Varity_R

0.49

gMVP

0.94

Mutation Taster

=84/16

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over