rs2278986

Positions:

• chr12-124814823-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005505.5(SCARB1):​c.426+150T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 943,434 control chromosomes in the GnomAD database, including 45,638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6327 hom., cov: 32)
  • Exomes 𝑓: 0.31 (39311 hom.)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.187

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 12-124814823-A-G is Benign according to our data. Variant chr12-124814823-A-G is described in ClinVar as [Benign]. Clinvar id is 1242016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-124814823-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCARB1	NM_005505.5	c.426+150T>C		intron_variant		ENST00000261693.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCARB1	ENST00000261693.11	c.426+150T>C		intron_variant		1	NM_005505.5	P3

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42746 AN: 152054 Hom.: 6312 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.308 AC: 243487 AN: 791262 Hom.: 39311 AF XY: 0.316 AC XY: 129676 AN XY: 410440

Gnomad4 AFR exome AF: 0.218

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.451

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.440

Gnomad4 FIN exome AF: 0.242

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.312

GnomAD4 genome AF: 0.281 AC: 42796 AN: 152172 Hom.: 6327 Cov.: 32 AF XY: 0.282 AC XY: 21014 AN XY: 74388

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.311

Alfa AF: 0.301 Hom.: 892

Bravo AF: 0.275

Asia WGS AF: 0.375 AC: 1301 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.52
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2278986; hg19: chr12-125299369; COSMIC: COSV55549668; COSMIC: COSV55549668;