Variant chr12-124778493-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001082959.2(SCARB1):c.1495G>A(p.Gly499Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,348,458 control chromosomes in the GnomAD database, including 1,264 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 789 hom., cov: 33)

Exomes 𝑓: 0.0051 ( 475 hom. )

Consequence

SCARB1
NM_001082959.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.743

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046088696).

BP6

Variant 12-124778493-C-T is Benign according to our data. Variant chr12-124778493-C-T is described in ClinVar as [Benign]. Clinvar id is 1297808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-124778493-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 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.*94G>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.*94G>A		3_prime_UTR_variant	13/13	1	NM_005505.5	ENSP00000261693.6		Q8WTV0-2

Frequencies

GnomAD3 genomes

AF:

0.0539

AC:

8192

AN:

151954

Hom.:

785

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0198

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.0350

GnomAD3 exomes

AF:

0.0140

AC:

424

AN:

30328

Hom.:

AF XY:

0.0113

AC XY:

169

AN XY:

14890

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.0171

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000108

Gnomad NFE exome

AF:

0.000909

Gnomad OTH exome

AF:

0.00797

GnomAD4 exome

AF:

0.00510

AC:

6101

AN:

1196384

Hom.:

475

Cov.:

AF XY:

0.00450

AC XY:

2596

AN XY:

576648

show subpopulations

Gnomad4 AFR exome

AF:

0.194

Gnomad4 AMR exome

AF:

0.0176

Gnomad4 ASJ exome

AF:

0.000424

Gnomad4 EAS exome

AF:

0.0000360

Gnomad4 SAS exome

AF:

0.000343

Gnomad4 FIN exome

AF:

0.0000957

Gnomad4 NFE exome

AF:

0.000602

Gnomad4 OTH exome

AF:

0.0125

GnomAD4 genome

AF:

0.0541

AC:

8227

AN:

152074

Hom.:

789

Cov.:

AF XY:

0.0525

AC XY:

3906

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.187

Gnomad4 AMR

AF:

0.0197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00116

Gnomad4 OTH

AF:

0.0347

Alfa

AF:

0.0327

Hom.:

Bravo

AF:

0.0624

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.158

AC:

644

ESP6500EA

AF:

0.00193

AC:

ExAC

AF:

0.0112

AC:

1227

Asia WGS

AF:

0.00837

AC:

AN:

3478

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 submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 01, 2019	This variant is associated with the following publications: (PMID: 27651445) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

1.7

DANN

Benign

0.96

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.1

PROVEAN

Benign

-0.51

REVEL

Benign

0.022

Sift

Benign

0.060

Sift4G

Benign

0.21

Vest4

0.060

MutPred

0.19

Gain of glycosylation at P497 (P = 0.071);

ClinPred

0.00078

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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