Genetic Variant SCARB1:c.726+54C>T (chr12-124811816-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.726+54C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0822 in 1,298,030 control chromosomes in the GnomAD database, including 5,172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 440 hom., cov: 32)

Exomes 𝑓: 0.085 ( 4732 hom. )

Consequence

SCARB1
NM_005505.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.80

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.07).

BP6

Variant 12-124811816-G-A is Benign according to our data. Variant chr12-124811816-G-A is described in ClinVar as [Benign]. Clinvar id is 1250072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB1	NM_005505.5 link	c.726+54C>T		intron_variant	Intron 5 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.726+54C>T		intron_variant	Intron 5 of 12	1	NM_005505.5	ENSP00000261693.6		Q8WTV0-2

Frequencies

GnomAD3 genomes

AF:

0.0618

AC:

9396

AN:

151948

Hom.:

440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0171

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.0711

Gnomad ASJ

AF:

0.0648

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0287

Gnomad FIN

AF:

0.0376

Gnomad MID

AF:

0.0892

Gnomad NFE

AF:

0.0974

Gnomad OTH

AF:

0.0693

GnomAD4 exome

AF:

0.0849

AC:

97260

AN:

1145964

Hom.:

4732

AF XY:

0.0834

AC XY:

48374

AN XY:

580350

show subpopulations

African (AFR)

AF:

0.0152

AC:

400

AN:

26302

American (AMR)

AF:

0.0519

AC:

2028

AN:

39102

Ashkenazi Jewish (ASJ)

AF:

0.0697

AC:

1658

AN:

23772

East Asian (EAS)

AF:

0.000141

AC:

AN:

35402

South Asian (SAS)

AF:

0.0304

AC:

2301

AN:

75746

European-Finnish (FIN)

AF:

0.0451

AC:

2254

AN:

49974

Middle Eastern (MID)

AF:

0.0750

AC:

390

AN:

5198

European-Non Finnish (NFE)

AF:

0.100

AC:

84407

AN:

840758

Other (OTH)

AF:

0.0768

AC:

3817

AN:

49710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

4584

9169

13753

18338

22922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0618

AC:

9391

AN:

152066

Hom.:

440

Cov.:

AF XY:

0.0577

AC XY:

4290

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0170

AC:

706

AN:

41494

American (AMR)

AF:

0.0710

AC:

1085

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0648

AC:

225

AN:

3470

East Asian (EAS)

AF:

0.00136

AC:

AN:

5166

South Asian (SAS)

AF:

0.0285

AC:

137

AN:

4804

European-Finnish (FIN)

AF:

0.0376

AC:

398

AN:

10594

Middle Eastern (MID)

AF:

0.0925

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0973

AC:

6614

AN:

67942

Other (OTH)

AF:

0.0686

AC:

145

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

453

906

1358

1811

2264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0322

Hom.:

Bravo

AF:

0.0622

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 10, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 10397692) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.26

(source)

DANN

Benign

0.90

PhyloP100

-4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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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12-124811816-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over