NM_005505.5:c.127-18597G>A

Variant names:

• chr12-124836304-C-T
• rs4765623
• NM_005505.5:c.127-18597G>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.127-18597G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 152,038 control chromosomes in the GnomAD database, including 11,469 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 0.38 (11469 hom., cov: 32)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 49 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 (AMR) allele frequency at 95% confidence interval = 0.498 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.127-18597G>A		intron	N/A	NP_005496.4
	SCARB1	NM_001367981.1		c.127-18597G>A		intron	N/A	NP_001354910.1	Q8WTV0-1
	SCARB1	NM_001367982.1		c.3+2940G>A		intron	N/A	NP_001354911.1	B3KW46

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	ENST00000261693.11	TSL:1 MANE Select	c.127-18597G>A		intron	N/A	ENSP00000261693.6	Q8WTV0-2
	SCARB1	ENST00000546215.5	TSL:1	c.127-18597G>A		intron	N/A	ENSP00000442862.1	B7ZKQ9
	SCARB1	ENST00000535005.5	TSL:1	n.442-18597G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58087 AN: 151920 Hom.: 11448 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.382 AC: 58144 AN: 152038 Hom.: 11469 Cov.: 32 AF XY: 0.384 AC XY: 28569 AN XY: 74308

African (AFR) AF: 0.413 AC: 17109 AN: 41448

American (AMR) AF: 0.507 AC: 7755 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1371 AN: 3472

East Asian (EAS) AF: 0.421 AC: 2179 AN: 5170

South Asian (SAS) AF: 0.403 AC: 1940 AN: 4816

European-Finnish (FIN) AF: 0.305 AC: 3226 AN: 10562

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23370 AN: 67980

Other (OTH) AF: 0.413 AC: 868 AN: 2104

Alfa AF: 0.358 Hom.: 37259

Bravo AF: 0.400

Asia WGS AF: 0.433 AC: 1506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.52
DANN	Benign	0.71
PhyloP100		-1.1
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: rs4765623; hg19: chr12-125320850;