12-124778493-C-T

Variant names:

• chr12-124778493-C-T
• rs701103
• NM_005505.5:c.*94G>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.*94G>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 0.0106 in 1,348,458 control chromosomes in the GnomAD database, including 1,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (789 hom., cov: 33)
  • Exomes 𝑓: 0.0051 (475 hom.)
• Consequence: SCARB1 NM_005505.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.743
• Publications: 9 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 (MetaRNN=0.0046088696).
• BP6: Variant 12-124778493-C-T is Benign according to our data. Variant chr12-124778493-C-T is described in ClinVar as [Benign]. Clinvar id is 1297808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.*94G>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.*94G>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.0539 AC: 8192 AN: 151954 Hom.: 785 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.00116

Gnomad OTH AF: 0.0350

GnomAD2 exomes AF: 0.0140 AC: 424 AN: 30328 AF XY: 0.0113

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.0171

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000108

Gnomad NFE exome AF: 0.000909

Gnomad OTH exome AF: 0.00797

GnomAD4 exome AF: 0.00510 AC: 6101 AN: 1196384 Hom.: 475 Cov.: 32 AF XY: 0.00450 AC XY: 2596 AN XY: 576648

African (AFR) AF: 0.194 AC: 4668 AN: 24036

American (AMR) AF: 0.0176 AC: 168 AN: 9568

Ashkenazi Jewish (ASJ) AF: 0.000424 AC: 7 AN: 16506

East Asian (EAS) AF: 0.0000360 AC: 1 AN: 27788

South Asian (SAS) AF: 0.000343 AC: 15 AN: 43736

European-Finnish (FIN) AF: 0.0000957 AC: 4 AN: 41802

Middle Eastern (MID) AF: 0.00957 AC: 41 AN: 4286

European-Non Finnish (NFE) AF: 0.000602 AC: 590 AN: 979938

Other (OTH) AF: 0.0125 AC: 607 AN: 48724

GnomAD4 genome AF: 0.0541 AC: 8227 AN: 152074 Hom.: 789 Cov.: 33 AF XY: 0.0525 AC XY: 3906 AN XY: 74342

African (AFR) AF: 0.187 AC: 7759 AN: 41438

American (AMR) AF: 0.0197 AC: 302 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4808

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10602

Middle Eastern (MID) AF: 0.0342 AC: 10 AN: 292

European-Non Finnish (NFE) AF: 0.00116 AC: 79 AN: 67968

Other (OTH) AF: 0.0347 AC: 73 AN: 2106

Alfa AF: 0.0355 Hom.: 100

Bravo AF: 0.0624

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.158 AC: 644

ESP6500EA AF: 0.00193 AC: 16

ExAC AF: 0.0112 AC: 1227

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Apr 01, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27651445) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.7
DANN	Benign	0.96
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.74
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.022
Sift	Benign	0.060	T
Sift4G	Benign	0.21	T
Vest4		0.060
MutPred		0.19		Gain of glycosylation at P497 (P = 0.071);
ClinPred		0.00078	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	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: rs701103; hg19: chr12-125263039; COSMIC: COSV55550572; COSMIC: COSV55550572;