chr12-124783886-G-A

Variant names:

• chr12-124783886-G-A
• rs838891
• NM_005505.5:c.1402-1075C>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.1402-1075C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,140 control chromosomes in the GnomAD database, including 30,032 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 0.62 (30031 hom., cov: 33)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.1402-1075C>T		intron_variant	Intron 11 of 12	ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.1402-1075C>T		intron_variant	Intron 11 of 12	1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94595 AN: 152014 Hom.: 30023 Cov.: 33

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.616

GnomAD4 exome AF: 0.500 AC: 4 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 4 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.750 AC: 3 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.622 AC: 94631 AN: 152132 Hom.: 30031 Cov.: 33 AF XY: 0.620 AC XY: 46136 AN XY: 74380

African (AFR) AF: 0.585 AC: 24276 AN: 41480

American (AMR) AF: 0.523 AC: 7988 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2449 AN: 3472

East Asian (EAS) AF: 0.334 AC: 1732 AN: 5178

South Asian (SAS) AF: 0.750 AC: 3621 AN: 4830

European-Finnish (FIN) AF: 0.637 AC: 6736 AN: 10574

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.673 AC: 45734 AN: 67990

Other (OTH) AF: 0.614 AC: 1299 AN: 2114

Alfa AF: 0.634 Hom.: 13727

Bravo AF: 0.609

Asia WGS AF: 0.551 AC: 1920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.065
DANN	Benign	0.65
PhyloP100		-1.7
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: rs838891; hg19: chr12-125268432;