12-124796556-G-T

Variant names:

• chr12-124796556-G-T
• rs1672879
• NM_005505.5:c.1129-1288C>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.1129-1288C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,134 control chromosomes in the GnomAD database, including 4,723 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 0.18 (4723 hom., cov: 33)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 11 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]

ENSG00000287242 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	NM_005505.5	MANE Select	c.1129-1288C>A		intron	N/A	NP_005496.4
	SCARB1	NM_001367981.1		c.1129-1288C>A		intron	N/A	NP_001354910.1
	SCARB1	NM_001367982.1		c.1006-1288C>A		intron	N/A	NP_001354911.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	ENST00000261693.11	TSL:1 MANE Select	c.1129-1288C>A		intron	N/A	ENSP00000261693.6
	SCARB1	ENST00000546215.5	TSL:1	c.1129-1288C>A		intron	N/A	ENSP00000442862.1
	SCARB1	ENST00000535005.5	TSL:1	n.1444-1288C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27340 AN: 152016 Hom.: 4689 Cov.: 33

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0863

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0449

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.0398

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.180 AC: 27433 AN: 152134 Hom.: 4723 Cov.: 33 AF XY: 0.180 AC XY: 13423 AN XY: 74366

African (AFR) AF: 0.427 AC: 17703 AN: 41462

American (AMR) AF: 0.208 AC: 3180 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0863 AC: 299 AN: 3466

East Asian (EAS) AF: 0.424 AC: 2187 AN: 5162

South Asian (SAS) AF: 0.106 AC: 509 AN: 4822

European-Finnish (FIN) AF: 0.0449 AC: 476 AN: 10612

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.0397 AC: 2702 AN: 68012

Other (OTH) AF: 0.157 AC: 331 AN: 2114

Alfa AF: 0.121 Hom.: 2422

Bravo AF: 0.206

Asia WGS AF: 0.256 AC: 888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.51
PhyloP100		-1.8
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: rs1672879; hg19: chr12-125281102;