Variant chr12-124814331-G-A 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_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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

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]

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=-0.82).

BP6

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

Synonymous conserved (PhyloP=-2.6 with no splicing effect.

BA1

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	Protein	UniProt
SCARB1	NM_005505.5 linkuse as main transcript	c.501C>T	p.Gly167=	synonymous_variant	4/13	ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11 linkuse as main transcript	c.501C>T	p.Gly167=	synonymous_variant	4/13	1	NM_005505.5	ENSP00000261693	P3	Q8WTV0-2

Frequencies

GnomAD3 genomes

AF:

0.0294

AC:

4467

AN:

152172

Hom.:

556

Cov.:

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.:

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

AF:

0.0293

AC:

4469

AN:

152290

Hom.:

557

Cov.:

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 26, 2018	This variant is associated with the following publications: (PMID: 28171541) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

SCARB1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 13, 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

-0.82

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.

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