rs2293440

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 15/18 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

Publications

12 publications found

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

new If you want to explore the variant's impact on the transcript NM_001367981.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 1246761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367981.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCARB1	NM_005505.5	MANE Select	c.1401+130T>C		intron	N/A	NP_005496.4
SCARB1	NM_001367981.1		c.1531T>C	p.Cys511Arg	missense	Exon 11 of 12	NP_001354910.1	Q8WTV0-1
SCARB1	NM_001367982.1		c.1408T>C	p.Cys470Arg	missense	Exon 11 of 11	NP_001354911.1	B3KW46

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCARB1	ENST00000261693.11	TSL:1 MANE Select	c.1401+130T>C	intron	N/A	ENSP00000261693.6	Q8WTV0-2
SCARB1	ENST00000546215.5	TSL:1	c.1317+214T>C	intron	N/A	ENSP00000442862.1	B7ZKQ9
SCARB1	ENST00000535005.5	TSL:1	n.1716+130T>C	intron	N/A

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

GnomAD2 exomes

AF:

0.128

AC:

29672

AN:

231230

AF XY:

0.112

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 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

African (AFR)

AF:

0.378

AC:

12657

AN:

33470

American (AMR)

AF:

0.254

AC:

11311

AN:

44574

Ashkenazi Jewish (ASJ)

AF:

0.0754

AC:

1967

AN:

26100

East Asian (EAS)

AF:

0.441

AC:

17492

AN:

39682

South Asian (SAS)

AF:

0.0752

AC:

6486

AN:

86218

European-Finnish (FIN)

AF:

0.0228

AC:

874

AN:

38392

Middle Eastern (MID)

AF:

0.122

AC:

705

AN:

5766

European-Non Finnish (NFE)

AF:

0.0309

AC:

34384

AN:

1111620

Other (OTH)

AF:

0.0942

AC:

5675

AN:

60248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

5192

10384

15577

20769

25961

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1760

3520

5280

7040

8800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.158

AC:

24058

AN:

152200

Hom.:

3690

Cov.:

AF XY:

0.159

AC XY:

11836

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.368

AC:

15276

AN:

41502

American (AMR)

AF:

0.194

AC:

2963

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0784

AC:

272

AN:

3470

East Asian (EAS)

AF:

0.419

AC:

2161

AN:

5156

South Asian (SAS)

AF:

0.0915

AC:

441

AN:

4820

European-Finnish (FIN)

AF:

0.0267

AC:

284

AN:

10618

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0342

AC:

2324

AN:

68018

Other (OTH)

AF:

0.142

AC:

300

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

878

1757

2635

3514

4392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

232

464

696

928

1160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0719

Hom.:

1310

Bravo

AF:

0.183

Asia WGS

AF:

0.250

AC:

868

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.6

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.043

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0078

LIST_S2

Benign

0.35

MetaRNN

Benign

0.00040

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

0.32

PROVEAN

Benign

-0.070

REVEL

Benign

0.045

Sift

Uncertain

0.013

Sift4G

Uncertain

0.036

Varity_R

0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over