12-124786544-G-C

Variant names:

• chr12-124786544-G-C
• rs838897
• NM_005505.5:c.1255-41C>G

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.1255-41C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.082 in 1,610,992 control chromosomes in the GnomAD database, including 14,095 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (3770 hom., cov: 33)
  • Exomes 𝑓: 0.073 (10325 hom.)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00600
• 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]

ENSG00000287242 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 12-124786544-G-C is Benign according to our data. Variant chr12-124786544-G-C is described in ClinVar as Benign. ClinVar VariationId is 1232985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.1255-41C>G		intron_variant	Intron 10 of 12	ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.1255-41C>G		intron_variant	Intron 10 of 12	1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25122 AN: 152122 Hom.: 3740 Cov.: 33

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0586

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0447

Gnomad OTH AF: 0.148

GnomAD2 exomes AF: 0.138 AC: 33822 AN: 245882 AF XY: 0.122

Gnomad AFR exome AF: 0.373

Gnomad AMR exome AF: 0.289

Gnomad ASJ exome AF: 0.0747

Gnomad EAS exome AF: 0.436

Gnomad FIN exome AF: 0.0588

Gnomad NFE exome AF: 0.0450

Gnomad OTH exome AF: 0.107

GnomAD4 exome AF: 0.0732 AC: 106831 AN: 1458752 Hom.: 10325 Cov.: 32 AF XY: 0.0719 AC XY: 52177 AN XY: 725670

African (AFR) AF: 0.372 AC: 12455 AN: 33456

American (AMR) AF: 0.279 AC: 12390 AN: 44450

Ashkenazi Jewish (ASJ) AF: 0.0759 AC: 1983 AN: 26122

East Asian (EAS) AF: 0.446 AC: 17695 AN: 39634

South Asian (SAS) AF: 0.0839 AC: 7231 AN: 86158

European-Finnish (FIN) AF: 0.0565 AC: 2900 AN: 51340

Middle Eastern (MID) AF: 0.136 AC: 785 AN: 5764

European-Non Finnish (NFE) AF: 0.0404 AC: 44936 AN: 1111488

Other (OTH) AF: 0.107 AC: 6456 AN: 60340

GnomAD4 genome AF: 0.166 AC: 25207 AN: 152240 Hom.: 3770 Cov.: 33 AF XY: 0.167 AC XY: 12408 AN XY: 74448

African (AFR) AF: 0.364 AC: 15123 AN: 41498

American (AMR) AF: 0.202 AC: 3093 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0793 AC: 275 AN: 3470

East Asian (EAS) AF: 0.429 AC: 2222 AN: 5180

South Asian (SAS) AF: 0.0991 AC: 479 AN: 4832

European-Finnish (FIN) AF: 0.0586 AC: 622 AN: 10616

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0446 AC: 3037 AN: 68032

Other (OTH) AF: 0.148 AC: 313 AN: 2114

Alfa AF: 0.102 Hom.: 307

Bravo AF: 0.190

Asia WGS AF: 0.264 AC: 919 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 01, 2018

GeneDx

Significance: 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	-0.79
CADD	Benign	1.0
DANN	Benign	0.61
PhyloP100		-0.0060
Mutation Taster		=100/0	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: rs838897; hg19: chr12-125271090; COSMIC: COSV55551195; COSMIC: COSV55551195;