chr12-124832845-C-A

Variant names:

• chr12-124832845-C-A
• rs10773107
• NM_005505.5:c.127-15138G>T

Variant summary

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

The NM_005505.5(SCARB1):​c.127-15138G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,816 control chromosomes in the GnomAD database, including 13,888 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 0.40 (13888 hom., cov: 31)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.127-15138G>T		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.127-15138G>T		intron_variant	Intron 1 of 12	1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61357 AN: 151698 Hom.: 13875 Cov.: 31

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.404 AC: 61395 AN: 151816 Hom.: 13888 Cov.: 31 AF XY: 0.406 AC XY: 30105 AN XY: 74200

African (AFR) AF: 0.188 AC: 7766 AN: 41394

American (AMR) AF: 0.463 AC: 7052 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1983 AN: 3468

East Asian (EAS) AF: 0.401 AC: 2071 AN: 5166

South Asian (SAS) AF: 0.510 AC: 2445 AN: 4798

European-Finnish (FIN) AF: 0.475 AC: 4994 AN: 10518

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.492 AC: 33439 AN: 67930

Other (OTH) AF: 0.458 AC: 962 AN: 2100

Alfa AF: 0.458 Hom.: 21043

Bravo AF: 0.392

Asia WGS AF: 0.441 AC: 1529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.81
PhyloP100		0.062
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: rs10773107; hg19: chr12-125317391;