Genetic Variant SCARB1:c.1401+1428A>G (chr12-124784929-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005505.5(SCARB1):c.1401+1428A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 152,320 control chromosomes in the GnomAD database, including 31,830 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.64 ( 31779 hom., cov: 34)

Exomes 𝑓: 0.74 ( 51 hom. )

Consequence

SCARB1
NM_005505.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.840

Publications

10 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005505.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCARB1	NM_005505.5	MANE Select	c.1401+1428A>G	intron	N/A	NP_005496.4
SCARB1	NM_001367981.1		c.1651+1178A>G	intron	N/A	NP_001354910.1	Q8WTV0-1
SCARB1	NM_001367983.1		c.1407+1428A>G	intron	N/A	NP_001354912.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCARB1	ENST00000261693.11	TSL:1 MANE Select	c.1401+1428A>G	intron	N/A	ENSP00000261693.6	Q8WTV0-2
SCARB1	ENST00000546215.5	TSL:1	c.1317+1512A>G	intron	N/A	ENSP00000442862.1	B7ZKQ9
SCARB1	ENST00000535005.5	TSL:1	n.1716+1428A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.641

AC:

97452

AN:

152008

Hom.:

31770

Cov.:

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.780

Gnomad AMR

AF:

0.533

Gnomad ASJ

AF:

0.716

Gnomad EAS

AF:

0.368

Gnomad SAS

AF:

0.762

Gnomad FIN

AF:

0.640

Gnomad MID

AF:

0.691

Gnomad NFE

AF:

0.688

Gnomad OTH

AF:

0.632

GnomAD4 exome

AF:

0.742

AC:

144

AN:

194

Hom.:

Cov.:

AF XY:

0.754

AC XY:

AN XY:

130

show subpopulations

African (AFR)

AF:

0.833

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.656

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.742

AC:

AN:

128

Other (OTH)

AF:

0.773

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.641

AC:

97489

AN:

152126

Hom.:

31779

Cov.:

AF XY:

0.638

AC XY:

47434

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.615

AC:

25509

AN:

41510

American (AMR)

AF:

0.532

AC:

8138

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.716

AC:

2483

AN:

3466

East Asian (EAS)

AF:

0.367

AC:

1900

AN:

5174

South Asian (SAS)

AF:

0.763

AC:

3687

AN:

4830

European-Finnish (FIN)

AF:

0.640

AC:

6782

AN:

10592

Middle Eastern (MID)

AF:

0.705

AC:

206

AN:

292

European-Non Finnish (NFE)

AF:

0.688

AC:

46746

AN:

67960

Other (OTH)

AF:

0.630

AC:

1328

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1801

3603

5404

7206

9007

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<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:

0.684

Hom.:

18296

Bravo

AF:

0.629

Asia WGS

AF:

0.575

AC:

2001

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

1.8

(source)

DANN

Benign

0.55

PhyloP100

-0.84

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

Publications

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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