chr12-124832579-G-A

Position:

• chr12-124832579-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005505.5(SCARB1):​c.127-14872C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 151,316 control chromosomes in the GnomAD database, including 828 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 0.099 (828 hom., cov: 33)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCARB1	NM_005505.5	c.127-14872C>T		intron_variant		ENST00000261693.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCARB1	ENST00000261693.11	c.127-14872C>T		intron_variant		1	NM_005505.5	P3

Frequencies

GnomAD3 genomes AF: 0.0985 AC: 14902 AN: 151242 Hom.: 829 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0694

Gnomad AMR AF: 0.0732

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0611

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.0986 AC: 14927 AN: 151316 Hom.: 828 Cov.: 33 AF XY: 0.0976 AC XY: 7207 AN XY: 73844

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0732

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0611

Gnomad4 NFE AF: 0.0815

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0865 Hom.: 871

Bravo AF: 0.102

Asia WGS AF: 0.141 AC: 490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs12581963; hg19: chr12-125317125;