rs7954519

Variant names:

• chr12-124835609-T-G
• rs7954519
• NM_005505.5:c.127-17902A>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.127-17902A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 151,724 control chromosomes in the GnomAD database, including 3,034 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 0.20 (3034 hom., cov: 31)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 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.127-17902A>C		intron	N/A	NP_005496.4
	SCARB1	NM_001367981.1		c.127-17902A>C		intron	N/A	NP_001354910.1	Q8WTV0-1
	SCARB1	NM_001367982.1		c.3+3635A>C		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.127-17902A>C		intron	N/A	ENSP00000261693.6	Q8WTV0-2
	SCARB1	ENST00000546215.5	TSL:1	c.127-17902A>C		intron	N/A	ENSP00000442862.1	B7ZKQ9
	SCARB1	ENST00000535005.5	TSL:1	n.442-17902A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29793 AN: 151604 Hom.: 3026 Cov.: 31

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.197 AC: 29833 AN: 151724 Hom.: 3034 Cov.: 31 AF XY: 0.195 AC XY: 14482 AN XY: 74130

African (AFR) AF: 0.228 AC: 9432 AN: 41370

American (AMR) AF: 0.135 AC: 2041 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 878 AN: 3468

East Asian (EAS) AF: 0.196 AC: 1004 AN: 5126

South Asian (SAS) AF: 0.173 AC: 829 AN: 4792

European-Finnish (FIN) AF: 0.186 AC: 1967 AN: 10558

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13016 AN: 67938

Other (OTH) AF: 0.183 AC: 385 AN: 2104

Alfa AF: 0.192 Hom.: 827

Bravo AF: 0.195

Asia WGS AF: 0.209 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.75
PhyloP100		-0.17
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: rs7954519; hg19: chr12-125320155;