Genetic Variant SCARB1:c.*1-112C>T (chr12-124778698-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005505.5(SCARB1):c.*1-112C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00717 in 956,776 control chromosomes in the GnomAD database, including 338 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 213 hom., cov: 0)

Exomes 𝑓: 0.0029 ( 125 hom. )

Consequence

SCARB1
NM_005505.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.34

Publications

1 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

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 12-124778698-G-A is Benign according to our data. Variant chr12-124778698-G-A is described in ClinVar as [Benign]. Clinvar id is 1254971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB1	NM_005505.5 link	c.*1-112C>T		intron_variant	Intron 12 of 12	ENST00000261693.11	NP_005496.4	Q8WTV0-2A0A024RBS4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11 link	c.*1-112C>T		intron_variant	Intron 12 of 12	1	NM_005505.5	ENSP00000261693.6		Q8WTV0-2

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

4172

AN:

39072

Hom.:

213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.282

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00705

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0625

Gnomad NFE

AF:

0.00273

Gnomad OTH

AF:

0.0779

GnomAD4 exome

AF:

0.00293

AC:

2687

AN:

917652

Hom.:

125

AF XY:

0.00263

AC XY:

1161

AN XY:

441174

show subpopulations

African (AFR)

AF:

0.106

AC:

2045

AN:

19356

American (AMR)

AF:

0.00956

AC:

AN:

8264

Ashkenazi Jewish (ASJ)

AF:

0.000513

AC:

AN:

13636

East Asian (EAS)

AF:

0.00

AC:

AN:

25644

South Asian (SAS)

AF:

0.000835

AC:

AN:

21554

European-Finnish (FIN)

AF:

0.0000337

AC:

AN:

29654

Middle Eastern (MID)

AF:

0.00787

AC:

AN:

2670

European-Non Finnish (NFE)

AF:

0.000283

AC:

215

AN:

758414

Other (OTH)

AF:

0.00783

AC:

301

AN:

38460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

122

244

365

487

609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.107

AC:

4177

AN:

39124

Hom.:

213

Cov.:

AF XY:

0.104

AC XY:

1954

AN XY:

18802

show subpopulations

African (AFR)

AF:

0.281

AC:

3925

AN:

13948

American (AMR)

AF:

0.0654

AC:

156

AN:

2386

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

878

East Asian (EAS)

AF:

0.00

AC:

AN:

1032

South Asian (SAS)

AF:

0.00704

AC:

AN:

1136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1820

Middle Eastern (MID)

AF:

0.0652

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00273

AC:

AN:

17192

Other (OTH)

AF:

0.0763

AC:

AN:

498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

168

336

504

672

840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0177

Hom.:

Bravo

AF:

0.0335

Asia WGS

AF:

0.00462

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

May 27, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.34

(source)

DANN

Benign

0.63

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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12-124778698-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over