3-52502648-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015136.3(STAB1):​c.504C>T​(p.His168=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0063 in 1,613,310 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 4 hom., cov: 33)
Exomes 𝑓: 0.0064 ( 70 hom. )

Consequence

STAB1
NM_015136.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.79
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
Variant 3-52502648-C-T is Benign according to our data. Variant chr3-52502648-C-T is described in ClinVar as [Benign]. Clinvar id is 767910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.79 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00503 (767/152338) while in subpopulation SAS AF= 0.023 (111/4828). AF 95% confidence interval is 0.0195. There are 4 homozygotes in gnomad4. There are 398 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
STAB1NM_015136.3 linkuse as main transcriptc.504C>T p.His168= synonymous_variant 6/69 ENST00000321725.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
STAB1ENST00000321725.10 linkuse as main transcriptc.504C>T p.His168= synonymous_variant 6/691 NM_015136.3 P1Q9NY15-1
STAB1ENST00000481607.1 linkuse as main transcriptn.559C>T non_coding_transcript_exon_variant 6/211

Frequencies

GnomAD3 genomes
AF:
0.00506
AC:
770
AN:
152220
Hom.:
4
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00499
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00360
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.00135
Gnomad SAS
AF:
0.0234
Gnomad FIN
AF:
0.00179
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00525
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00630
AC:
1579
AN:
250594
Hom.:
13
AF XY:
0.00733
AC XY:
995
AN XY:
135674
show subpopulations
Gnomad AFR exome
AF:
0.00463
Gnomad AMR exome
AF:
0.00234
Gnomad ASJ exome
AF:
0.00159
Gnomad EAS exome
AF:
0.000816
Gnomad SAS exome
AF:
0.0251
Gnomad FIN exome
AF:
0.00171
Gnomad NFE exome
AF:
0.00503
Gnomad OTH exome
AF:
0.00295
GnomAD4 exome
AF:
0.00644
AC:
9402
AN:
1460972
Hom.:
70
Cov.:
32
AF XY:
0.00699
AC XY:
5076
AN XY:
726682
show subpopulations
Gnomad4 AFR exome
AF:
0.00505
Gnomad4 AMR exome
AF:
0.00230
Gnomad4 ASJ exome
AF:
0.00161
Gnomad4 EAS exome
AF:
0.000655
Gnomad4 SAS exome
AF:
0.0247
Gnomad4 FIN exome
AF:
0.00162
Gnomad4 NFE exome
AF:
0.00579
Gnomad4 OTH exome
AF:
0.00620
GnomAD4 genome
AF:
0.00503
AC:
767
AN:
152338
Hom.:
4
Cov.:
33
AF XY:
0.00534
AC XY:
398
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.00498
Gnomad4 AMR
AF:
0.00359
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.00135
Gnomad4 SAS
AF:
0.0230
Gnomad4 FIN
AF:
0.00179
Gnomad4 NFE
AF:
0.00523
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.00460
Hom.:
2
Bravo
AF:
0.00437
Asia WGS
AF:
0.00866
AC:
30
AN:
3478
EpiCase
AF:
0.00431
EpiControl
AF:
0.00563

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
CADD
Benign
0.48
DANN
Benign
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs140965743; hg19: chr3-52536664; COSMIC: COSV58734964; COSMIC: COSV58734964; API