Variant 12-124800202-A-G 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.1050T>C(p.Ala350=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,612,832 control chromosomes in the GnomAD database, including 248,441 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 31231 hom., cov: 32)

Exomes 𝑓: 0.54 ( 217210 hom. )

Consequence

SCARB1
NM_005505.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -6.31

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 12-124800202-A-G is Benign according to our data. Variant chr12-124800202-A-G is described in ClinVar as [Benign]. Clinvar id is 1236346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-124800202-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-6.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 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.1050T>C	p.Ala350=	synonymous_variant	8/13	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.1050T>C	p.Ala350=	synonymous_variant	8/13	1	NM_005505.5	ENSP00000261693	P3	Q8WTV0-2
	ENST00000657226.1 linkuse as main transcript	n.1126-7408A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.627

AC:

95273

AN:

151928

Hom.:

31181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.812

Gnomad AMI

AF:

0.557

Gnomad AMR

AF:

0.641

Gnomad ASJ

AF:

0.430

Gnomad EAS

AF:

0.749

Gnomad SAS

AF:

0.544

Gnomad FIN

AF:

0.608

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.523

Gnomad OTH

AF:

0.605

GnomAD3 exomes

AF:

0.588

AC:

147686

AN:

251150

Hom.:

44658

AF XY:

0.576

AC XY:

78145

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.816

Gnomad AMR exome

AF:

0.685

Gnomad ASJ exome

AF:

0.429

Gnomad EAS exome

AF:

0.752

Gnomad SAS exome

AF:

0.533

Gnomad FIN exome

AF:

0.600

Gnomad NFE exome

AF:

0.528

Gnomad OTH exome

AF:

0.559

GnomAD4 exome

AF:

0.541

AC:

789584

AN:

1460786

Hom.:

217210

Cov.:

AF XY:

0.538

AC XY:

391323

AN XY:

726740

show subpopulations

Gnomad4 AFR exome

AF:

0.822

Gnomad4 AMR exome

AF:

0.681

Gnomad4 ASJ exome

AF:

0.426

Gnomad4 EAS exome

AF:

0.765

Gnomad4 SAS exome

AF:

0.533

Gnomad4 FIN exome

AF:

0.592

Gnomad4 NFE exome

AF:

0.519

Gnomad4 OTH exome

AF:

0.553

GnomAD4 genome

AF:

0.627

AC:

95381

AN:

152046

Hom.:

31231

Cov.:

AF XY:

0.630

AC XY:

46829

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.812

Gnomad4 AMR

AF:

0.641

Gnomad4 ASJ

AF:

0.430

Gnomad4 EAS

AF:

0.749

Gnomad4 SAS

AF:

0.545

Gnomad4 FIN

AF:

0.608

Gnomad4 NFE

AF:

0.523

Gnomad4 OTH

AF:

0.603

Alfa

AF:

0.528

Hom.:

24928

Bravo

AF:

0.640

Asia WGS

AF:

0.638

AC:

2218

AN:

3478

EpiCase

AF:

0.519

EpiControl

AF:

0.518

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	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	This variant is associated with the following publications: (PMID: 27651445, 23510561, 28008009, 12519372, 19806217, 17476110, 10397692, 20060115) -
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

-0.98

CADD

Benign

0.018

DANN

Benign

0.38

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