12-124833036-C-T

Variant names:

• chr12-124833036-C-T
• rs10744182
• NM_005505.5:c.127-15329G>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.127-15329G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,598 control chromosomes in the GnomAD database, including 20,217 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 0.50 (20217 hom., cov: 29)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 9 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005505.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	NM_005505.5	MANE Select	c.127-15329G>A		intron	N/A	NP_005496.4
	SCARB1	NM_001367981.1		c.127-15329G>A		intron	N/A	NP_001354910.1
	SCARB1	NM_001367982.1		c.3+6208G>A		intron	N/A	NP_001354911.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	ENST00000261693.11	TSL:1 MANE Select	c.127-15329G>A		intron	N/A	ENSP00000261693.6
	SCARB1	ENST00000546215.5	TSL:1	c.127-15329G>A		intron	N/A	ENSP00000442862.1
	SCARB1	ENST00000535005.5	TSL:1	n.442-15329G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75065 AN: 151480 Hom.: 20219 Cov.: 29

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.495 AC: 75063 AN: 151598 Hom.: 20217 Cov.: 29 AF XY: 0.497 AC XY: 36830 AN XY: 74066

African (AFR) AF: 0.272 AC: 11220 AN: 41290

American (AMR) AF: 0.547 AC: 8325 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2312 AN: 3466

East Asian (EAS) AF: 0.421 AC: 2154 AN: 5116

South Asian (SAS) AF: 0.566 AC: 2714 AN: 4794

European-Finnish (FIN) AF: 0.608 AC: 6396 AN: 10524

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.587 AC: 39862 AN: 67876

Other (OTH) AF: 0.568 AC: 1196 AN: 2104

Alfa AF: 0.567 Hom.: 23476

Bravo AF: 0.480

Asia WGS AF: 0.489 AC: 1698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.26
DANN	Benign	0.38
PhyloP100		-2.3
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: rs10744182; hg19: chr12-125317582;