rs188375019

Variant names:

• chr12-124778729-G-A
• rs188375019
• NM_005505.5:c.*1-143C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005505.5(SCARB1):​c.*1-143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 846,792 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (10 hom., cov: 31)
  • Exomes 𝑓: 0.00056 (5 hom.)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.66
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 12-124778729-G-A is Benign according to our data. Variant chr12-124778729-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1316819.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00621 (910/146434) while in subpopulation AFR AF = 0.0216 (856/39550). AF 95% confidence interval is 0.0204. There are 10 homozygotes in GnomAd4. There are 419 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.*1-143C>T		intron_variant	Intron 12 of 12	ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.*1-143C>T		intron_variant	Intron 12 of 12	1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.00618 AC: 905 AN: 146328 Hom.: 10 Cov.: 31

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00276

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00327

Gnomad NFE AF: 0.000104

Gnomad OTH AF: 0.00396

GnomAD4 exome AF: 0.000555 AC: 389 AN: 700358 Hom.: 5 AF XY: 0.000483 AC XY: 166 AN XY: 343600

African (AFR) AF: 0.0200 AC: 298 AN: 14904

American (AMR) AF: 0.00224 AC: 18 AN: 8048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12598

East Asian (EAS) AF: 0.00 AC: 0 AN: 24686

South Asian (SAS) AF: 0.00 AC: 0 AN: 21902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27580

Middle Eastern (MID) AF: 0.00130 AC: 3 AN: 2302

European-Non Finnish (NFE) AF: 0.0000305 AC: 17 AN: 556578

Other (OTH) AF: 0.00167 AC: 53 AN: 31760

GnomAD4 genome AF: 0.00621 AC: 910 AN: 146434 Hom.: 10 Cov.: 31 AF XY: 0.00591 AC XY: 419 AN XY: 70916

African (AFR) AF: 0.0216 AC: 856 AN: 39550

American (AMR) AF: 0.00276 AC: 38 AN: 13788

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 4816

South Asian (SAS) AF: 0.00 AC: 0 AN: 4650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9594

Middle Eastern (MID) AF: 0.00355 AC: 1 AN: 282

European-Non Finnish (NFE) AF: 0.000104 AC: 7 AN: 67368

Other (OTH) AF: 0.00392 AC: 8 AN: 2042

Alfa AF: 0.00520 Hom.: 1

Bravo AF: 0.00698

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 21, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.5
DANN	Benign	0.75
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs188375019; hg19: chr12-125263275;