Variant chr12-124786227-A-G 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_001367981.1(SCARB1):c.1531T>C(p.Cys511Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 1,598,270 control chromosomes in the GnomAD database, including 13,066 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 3690 hom., cov: 33)

Exomes 𝑓: 0.063 ( 9376 hom. )

Consequence

SCARB1
NM_001367981.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.324

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.0113926E-4).

BP6

Variant 12-124786227-A-G is Benign according to our data. Variant chr12-124786227-A-G is described in ClinVar as [Benign]. Clinvar id is 1246761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-124786227-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB1	NM_005505.5 link	c.1401+130T>C		intron_variant		ENST00000261693.11	NP_005496.4	Q8WTV0-2A0A024RBS4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11 link	c.1401+130T>C		intron_variant		1	NM_005505.5	ENSP00000261693.6		Q8WTV0-2

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

23974

AN:

152082

Hom.:

3666

Cov.:

show subpopulations

Gnomad AFR

AF:

0.367

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.0784

Gnomad EAS

AF:

0.418

Gnomad SAS

AF:

0.0922

Gnomad FIN

AF:

0.0267

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0342

Gnomad OTH

AF:

0.141

GnomAD3 exomes

AF:

0.128

AC:

29672

AN:

231230

Hom.:

4221

AF XY:

0.112

AC XY:

14320

AN XY:

127354

show subpopulations

Gnomad AFR exome

AF:

0.375

Gnomad AMR exome

AF:

0.264

Gnomad ASJ exome

AF:

0.0746

Gnomad EAS exome

AF:

0.431

Gnomad SAS exome

AF:

0.0745

Gnomad FIN exome

AF:

0.0226

Gnomad NFE exome

AF:

0.0350

Gnomad OTH exome

AF:

0.0932

GnomAD4 exome

AF:

0.0633

AC:

91551

AN:

1446070

Hom.:

9376

Cov.:

AF XY:

0.0620

AC XY:

44614

AN XY:

719732

show subpopulations

Gnomad4 AFR exome

AF:

0.378

Gnomad4 AMR exome

AF:

0.254

Gnomad4 ASJ exome

AF:

0.0754

Gnomad4 EAS exome

AF:

0.441

Gnomad4 SAS exome

AF:

0.0752

Gnomad4 FIN exome

AF:

0.0228

Gnomad4 NFE exome

AF:

0.0309

Gnomad4 OTH exome

AF:

0.0942

GnomAD4 genome

AF:

0.158

AC:

24058

AN:

152200

Hom.:

3690

Cov.:

AF XY:

0.159

AC XY:

11836

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.368

Gnomad4 AMR

AF:

0.194

Gnomad4 ASJ

AF:

0.0784

Gnomad4 EAS

AF:

0.419

Gnomad4 SAS

AF:

0.0915

Gnomad4 FIN

AF:

0.0267

Gnomad4 NFE

AF:

0.0342

Gnomad4 OTH

AF:

0.142

Alfa

AF:

0.0624

Hom.:

646

Bravo

AF:

0.183

TwinsUK

AF:

0.0345

AC:

128

ALSPAC

AF:

0.0265

AC:

102

ExAC

AF:

0.116

AC:

14024

Asia WGS

AF:

0.250

AC:

868

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	Oct 01, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.6

DANN

Benign

0.65

DEOGEN2

Benign

0.043

T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0078

LIST_S2

Benign

0.35

T;T

MetaRNN

Benign

0.00040

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;.

PROVEAN

Benign

-0.070

N;N

REVEL

Benign

0.045

Sift

Uncertain

0.013

D;D

Sift4G

Uncertain

0.036

D;D

Polyphen

0.0

B;.

Vest4

0.077

ClinPred

0.0020

GERP RS

0.13

Varity_R

0.19

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