rs2343394

Variant names:

• chr12-124816005-G-A
• rs2343394
• NM_005505.5:c.285-891C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-124816005-G-A
• chr12-124816005-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005505.5(SCARB1):​c.285-891C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 151,544 control chromosomes in the GnomAD database, including 5,883 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 0.27 (5883 hom., cov: 32)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.423 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.285-891C>T		intron	N/A	NP_005496.4
	SCARB1	NM_001367981.1		c.285-891C>T		intron	N/A	NP_001354910.1
	SCARB1	NM_001367982.1		c.162-891C>T		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.285-891C>T		intron	N/A	ENSP00000261693.6
	SCARB1	ENST00000546215.5	TSL:1	c.285-891C>T		intron	N/A	ENSP00000442862.1
	SCARB1	ENST00000535005.5	TSL:1	n.600-891C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41128 AN: 151426 Hom.: 5874 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.272 AC: 41164 AN: 151544 Hom.: 5883 Cov.: 32 AF XY: 0.273 AC XY: 20210 AN XY: 74080

African (AFR) AF: 0.201 AC: 8249 AN: 41080

American (AMR) AF: 0.242 AC: 3695 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1555 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1149 AN: 5170

South Asian (SAS) AF: 0.438 AC: 2110 AN: 4814

European-Finnish (FIN) AF: 0.238 AC: 2514 AN: 10550

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20743 AN: 67890

Other (OTH) AF: 0.301 AC: 634 AN: 2108

Alfa AF: 0.172 Hom.: 386

Bravo AF: 0.263

Asia WGS AF: 0.366 AC: 1270 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	0.44
DANN	Benign	0.85
PhyloP100		-0.76
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: rs2343394; hg19: chr12-125300551;