Genetic Variant SCARB1:c.726+54C>G (chr12-124811816-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005505.5(SCARB1):c.726+54C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000381 in 1,298,844 control chromosomes in the GnomAD database, including 2 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 0.0023 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

SCARB1
NM_005505.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.80

Publications

16 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.06).

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.726+54C>G	intron	N/A	NP_005496.4
SCARB1	NM_001367981.1		c.726+54C>G	intron	N/A	NP_001354910.1	Q8WTV0-1
SCARB1	NM_001367982.1		c.603+54C>G	intron	N/A	NP_001354911.1	B3KW46

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCARB1	ENST00000261693.11	TSL:1 MANE Select	c.726+54C>G	intron	N/A	ENSP00000261693.6	Q8WTV0-2
SCARB1	ENST00000546215.5	TSL:1	c.726+54C>G	intron	N/A	ENSP00000442862.1	B7ZKQ9
SCARB1	ENST00000535005.5	TSL:1	n.1041+54C>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00223

AC:

339

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00776

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00382

GnomAD4 exome

AF:

0.000127

AC:

146

AN:

1146760

Hom.:

AF XY:

0.000102

AC XY:

AN XY:

580722

show subpopulations

African (AFR)

AF:

0.00403

AC:

106

AN:

26288

American (AMR)

AF:

0.000358

AC:

AN:

39104

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23780

East Asian (EAS)

AF:

0.000169

AC:

AN:

35400

South Asian (SAS)

AF:

0.0000264

AC:

AN:

75754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49998

Middle Eastern (MID)

AF:

0.000385

AC:

AN:

5198

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

841514

Other (OTH)

AF:

0.000282

AC:

AN:

49724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.407

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.00229

AC:

349

AN:

152084

Hom.:

Cov.:

AF XY:

0.00234

AC XY:

174

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.00798

AC:

331

AN:

41492

American (AMR)

AF:

0.000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67962

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00301

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.084

(source)

DANN

Benign

0.26

PhyloP100

-4.8

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

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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