12-124806310-A-T

Variant names:

• chr12-124806310-A-T
• rs865716
• NM_005505.5:c.1009+1451T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005505.5(SCARB1):​c.1009+1451T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,812 control chromosomes in the GnomAD database, including 26,388 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (26388 hom., cov: 30)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• 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]

ENSG00000287242 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.1009+1451T>A		intron_variant	Intron 7 of 12	ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.1009+1451T>A		intron_variant	Intron 7 of 12	1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88208 AN: 151696 Hom.: 26332 Cov.: 30

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.569

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.582 AC: 88325 AN: 151812 Hom.: 26388 Cov.: 30 AF XY: 0.586 AC XY: 43482 AN XY: 74210

African (AFR) AF: 0.688 AC: 28495 AN: 41388

American (AMR) AF: 0.621 AC: 9464 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1438 AN: 3468

East Asian (EAS) AF: 0.777 AC: 4006 AN: 5154

South Asian (SAS) AF: 0.533 AC: 2558 AN: 4800

European-Finnish (FIN) AF: 0.591 AC: 6235 AN: 10548

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.505 AC: 34311 AN: 67910

Other (OTH) AF: 0.569 AC: 1197 AN: 2104

Alfa AF: 0.557 Hom.: 2691

Bravo AF: 0.593

Asia WGS AF: 0.626 AC: 2179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.82
PhyloP100		-1.2
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: rs865716; hg19: chr12-125290856;