dbSNP rs529062376: STAB1:p.Ala212Thr (chr3-52503049-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015136.3(STAB1):c.634G>A(p.Ala212Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 1,603,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. A212S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

STAB1
NM_015136.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.680

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040192336).

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.634G>A	p.Ala212Thr	missense	Exon 7 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.634G>A	p.Ala212Thr	missense	Exon 7 of 69	ENSP00000312946.6	Q9NY15-1
STAB1	ENST00000481607.1	TSL:1	n.689G>A		non_coding_transcript_exon	Exon 7 of 21
STAB1	ENST00000899926.1		c.634G>A	p.Ala212Thr	missense	Exon 7 of 69	ENSP00000569985.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152238

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:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000302

AC:

AN:

231644

AF XY:

0.0000318

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000572

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000479

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000152

AC:

AN:

1451404

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

721034

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33380

American (AMR)

AF:

0.00

AC:

AN:

43656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25912

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39372

South Asian (SAS)

AF:

0.0000237

AC:

AN:

84246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51180

Middle Eastern (MID)

AF:

0.000188

AC:

AN:

5330

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1108296

Other (OTH)

AF:

0.0000167

AC:

AN:

60032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41470

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000248

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.8

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.058

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.74

M_CAP

Benign

0.0040

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.3

PhyloP100

0.68

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.16

REVEL

Benign

0.026

Sift

Benign

0.59

Sift4G

Benign

0.32

Polyphen

0.029

Vest4

0.12

MutPred

0.22

Gain of glycosylation at A212 (P = 0.0141)

MVP

0.40

MPC

0.20

ClinPred

0.038

GERP RS

3.2

Varity_R

0.051

gMVP

0.49

Mutation Taster

=92/8

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over