12-124778515-C-T

Variant names:

• chr12-124778515-C-T
• rs3825140
• NM_005505.5:c.*72G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005505.5(SCARB1):​c.*72G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 1,230,548 control chromosomes in the GnomAD database, including 3,453 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (512 hom., cov: 33)
  • Exomes 𝑓: 0.016 (2941 hom.)
• Consequence: SCARB1 NM_005505.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.08
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 12-124778515-C-T is Benign according to our data. Variant chr12-124778515-C-T is described in ClinVar as [Benign]. Clinvar id is 1181016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.*72G>A		3_prime_UTR_variant	Exon 13 of 13	ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.*72G>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.0302 AC: 4557 AN: 150788 Hom.: 512 Cov.: 33

Gnomad AFR AF: 0.00458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.00289

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.0323

Gnomad FIN AF: 0.00915

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00216

Gnomad OTH AF: 0.0371

GnomAD2 exomes AF: 0.0250 AC: 661 AN: 26458 AF XY: 0.0239

Gnomad AFR exome AF: 0.00278

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.00255

Gnomad EAS exome AF: 0.415

Gnomad FIN exome AF: 0.00993

Gnomad NFE exome AF: 0.00313

Gnomad OTH exome AF: 0.0308

GnomAD4 exome AF: 0.0155 AC: 16786 AN: 1079628 Hom.: 2941 Cov.: 32 AF XY: 0.0156 AC XY: 8109 AN XY: 521334

African (AFR) AF: 0.00242 AC: 52 AN: 21500

American (AMR) AF: 0.169 AC: 1362 AN: 8046

Ashkenazi Jewish (ASJ) AF: 0.00292 AC: 41 AN: 14056

East Asian (EAS) AF: 0.462 AC: 12059 AN: 26076

South Asian (SAS) AF: 0.0188 AC: 823 AN: 43764

European-Finnish (FIN) AF: 0.00973 AC: 335 AN: 34426

Middle Eastern (MID) AF: 0.00360 AC: 13 AN: 3608

European-Non Finnish (NFE) AF: 0.000948 AC: 839 AN: 885034

Other (OTH) AF: 0.0293 AC: 1262 AN: 43118

GnomAD4 genome AF: 0.0302 AC: 4565 AN: 150920 Hom.: 512 Cov.: 33 AF XY: 0.0348 AC XY: 2568 AN XY: 73710

African (AFR) AF: 0.00456 AC: 188 AN: 41196

American (AMR) AF: 0.125 AC: 1903 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.00289 AC: 10 AN: 3464

East Asian (EAS) AF: 0.394 AC: 1994 AN: 5064

South Asian (SAS) AF: 0.0321 AC: 148 AN: 4614

European-Finnish (FIN) AF: 0.00915 AC: 95 AN: 10388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00216 AC: 146 AN: 67736

Other (OTH) AF: 0.0386 AC: 81 AN: 2098

Alfa AF: 0.0238 Hom.: 167

Bravo AF: 0.0396

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

SCARB1-related disorder Benign:1

Jul 08, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.24
DANN	Benign	0.67
PhyloP100		-3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3825140; hg19: chr12-125263061; COSMIC: COSV55552447; COSMIC: COSV55552447;