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GeneBe

rs5889

chr12-124814331-G-Achr12-124814331-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005505.5(SCARB1):c.501C>T(p.Gly167=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 1,614,134 control chromosomes in the GnomAD database, including 5,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 557 hom., cov: 32)
Exomes 𝑓: 0.023 ( 5279 hom. )

Consequence

SCARB1
NM_005505.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.60
Variant links:
Genes affected
SCARB1 (HGNC:1664): (scavenger receptor class B member 1) The protein encoded by this gene is a plasma membrane receptor for high density lipoprotein cholesterol (HDL). The encoded protein mediates cholesterol transfer to and from HDL. In addition, this protein is a receptor for hepatitis C virus glycoprotein E2 and facilitates cell entry by the virus, SARS-CoV2. [provided by RefSeq, Oct 2021]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-124814331-G-A is Benign according to our data. Variant chr12-124814331-G-A is described in ClinVar as [Benign]. Clinvar id is 1283188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-124814331-G-A is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.6 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCARB1NM_005505.5 linkuse as main transcriptc.501C>T p.Gly167= synonymous_variant 4/13 ENST00000261693.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCARB1ENST00000261693.11 linkuse as main transcriptc.501C>T p.Gly167= synonymous_variant 4/131 NM_005505.5 P3Q8WTV0-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0294
AC:
4467
AN:
152172
Hom.:
556
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00367
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.108
Gnomad ASJ
AF:
0.00346
Gnomad EAS
AF:
0.398
Gnomad SAS
AF:
0.0553
Gnomad FIN
AF:
0.00904
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00225
Gnomad OTH
AF:
0.0315
GnomAD3 exomes
AF:
0.0637
AC:
16024
AN:
251470
Hom.:
2306
AF XY:
0.0558
AC XY:
7589
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.00326
Gnomad AMR exome
AF:
0.192
Gnomad ASJ exome
AF:
0.00288
Gnomad EAS exome
AF:
0.403
Gnomad SAS exome
AF:
0.0400
Gnomad FIN exome
AF:
0.00868
Gnomad NFE exome
AF:
0.00193
Gnomad OTH exome
AF:
0.0389
GnomAD4 exome
AF:
0.0225
AC:
32921
AN:
1461844
Hom.:
5279
Cov.:
32
AF XY:
0.0223
AC XY:
16204
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.00251
Gnomad4 AMR exome
AF:
0.179
Gnomad4 ASJ exome
AF:
0.00272
Gnomad4 EAS exome
AF:
0.456
Gnomad4 SAS exome
AF:
0.0388
Gnomad4 FIN exome
AF:
0.00812
Gnomad4 NFE exome
AF:
0.00101
Gnomad4 OTH exome
AF:
0.0287
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0293
AC:
4469
AN:
152290
Hom.:
557
Cov.:
32
AF XY:
0.0342
AC XY:
2543
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.00366
Gnomad4 AMR
AF:
0.109
Gnomad4 ASJ
AF:
0.00346
Gnomad4 EAS
AF:
0.399
Gnomad4 SAS
AF:
0.0552
Gnomad4 FIN
AF:
0.00904
Gnomad4 NFE
AF:
0.00225
Gnomad4 OTH
AF:
0.0307
Alfa
AF:
0.0131
Hom.:
503
Bravo
AF:
0.0387
Asia WGS
AF:
0.163
AC:
565
AN:
3478
EpiCase
AF:
0.00120
EpiControl
AF:
0.00154

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxOct 26, 2018This variant is associated with the following publications: (PMID: 28171541) -
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
SCARB1-related condition Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMar 13, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
Cadd
Benign
0.69
Dann
Benign
0.47
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

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

Other links and lift over

dbSNP: rs5889; hg19: chr12-125298877; COSMIC: COSV55547864; COSMIC: COSV55547864; API