Variant chr12-124778515-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001082959.2(SCARB1):c.1473G>A(p.Pro491Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 1,230,548 control chromosomes in the GnomAD database, including 3,453 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 512 hom., cov: 33)

Exomes 𝑓: 0.016 ( 2941 hom. )

Consequence

SCARB1
NM_001082959.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.08

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]

SCARB1 links:

SCARB1 (HGNC:):

SCARB1 links:

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=-0.77).

BP6

Variant 12-124778515-C-T is Benign according to our data. Variant chr12-124778515-C-T is described in ClinVar as [Benign]. Clinvar id is 1181016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-124778515-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB1	NM_005505.5 linkuse as main transcript	c.*72G>A		3_prime_UTR_variant	13/13	ENST00000261693.11	NP_005496.4	Q8WTV0-2A0A024RBS4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11 linkuse as main transcript	c.*72G>A		3_prime_UTR_variant	13/13	1	NM_005505.5	ENSP00000261693.6		Q8WTV0-2

Frequencies

GnomAD3 genomes

AF:

0.0302

AC:

4557

AN:

150788

Hom.:

512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.393

Gnomad SAS

AF:

0.0323

Gnomad FIN

AF:

0.00915

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00216

Gnomad OTH

AF:

0.0371

GnomAD3 exomes

AF:

0.0250

AC:

661

AN:

26458

Hom.:

AF XY:

0.0239

AC XY:

317

AN XY:

13238

show subpopulations

Gnomad AFR exome

AF:

0.00278

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.00255

Gnomad EAS exome

AF:

0.415

Gnomad SAS exome

AF:

0.0227

Gnomad FIN exome

AF:

0.00993

Gnomad NFE exome

AF:

0.00313

Gnomad OTH exome

AF:

0.0308

GnomAD4 exome

AF:

0.0155

AC:

16786

AN:

1079628

Hom.:

2941

Cov.:

AF XY:

0.0156

AC XY:

8109

AN XY:

521334

show subpopulations

Gnomad4 AFR exome

AF:

0.00242

Gnomad4 AMR exome

AF:

0.169

Gnomad4 ASJ exome

AF:

0.00292

Gnomad4 EAS exome

AF:

0.462

Gnomad4 SAS exome

AF:

0.0188

Gnomad4 FIN exome

AF:

0.00973

Gnomad4 NFE exome

AF:

0.000948

Gnomad4 OTH exome

AF:

0.0293

GnomAD4 genome

AF:

0.0302

AC:

4565

AN:

150920

Hom.:

512

Cov.:

AF XY:

0.0348

AC XY:

2568

AN XY:

73710

show subpopulations

Gnomad4 AFR

AF:

0.00456

Gnomad4 AMR

AF:

0.125

Gnomad4 ASJ

AF:

0.00289

Gnomad4 EAS

AF:

0.394

Gnomad4 SAS

AF:

0.0321

Gnomad4 FIN

AF:

0.00915

Gnomad4 NFE

AF:

0.00216

Gnomad4 OTH

AF:

0.0386

Alfa

AF:

0.0254

Hom.:

159

Bravo

AF:

0.0396

Asia WGS

AF:

0.154

AC:

535

AN:

3478

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 submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 17, 2018	- -

SCARB1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 08, 2019

This 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

-0.77

CADD

Benign

0.24

DANN

Benign

0.67

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over