12-124842858-C-T

Variant names:

• chr12-124842858-C-T
• rs12370382
• NM_005505.5:c.126+20737G>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.126+20737G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,136 control chromosomes in the GnomAD database, including 8,053 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 0.30 (8053 hom., cov: 33)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.126+20737G>A		intron_variant	Intron 1 of 12	ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.126+20737G>A		intron_variant	Intron 1 of 12	1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46388 AN: 152018 Hom.: 8058 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.305 AC: 46384 AN: 152136 Hom.: 8053 Cov.: 33 AF XY: 0.305 AC XY: 22646 AN XY: 74368

African (AFR) AF: 0.134 AC: 5548 AN: 41504

American (AMR) AF: 0.314 AC: 4799 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1131 AN: 3472

East Asian (EAS) AF: 0.307 AC: 1586 AN: 5160

South Asian (SAS) AF: 0.381 AC: 1838 AN: 4822

European-Finnish (FIN) AF: 0.363 AC: 3837 AN: 10578

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.389 AC: 26463 AN: 68002

Other (OTH) AF: 0.319 AC: 674 AN: 2114

Alfa AF: 0.355 Hom.: 4156

Bravo AF: 0.292

Asia WGS AF: 0.289 AC: 1006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.6
DANN	Benign	0.38
PhyloP100		-0.033
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: rs12370382; hg19: chr12-125327404;