12-124866570-T-C

Variant names:

• chr12-124866570-T-C
• rs4379922
• ENST00000535005.5:n.441+419A>G

Variant summary

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

The ENST00000535005.5(SCARB1):​n.441+419A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,006 control chromosomes in the GnomAD database, including 10,580 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 0.36 (10580 hom., cov: 32)
• Consequence: SCARB1 ENST00000535005.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 12 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]

LOC105370050 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000535005.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	ENST00000535005.5	TSL:1	n.441+419A>G		intron	N/A
	SCARB1	ENST00000541661.5	TSL:5	n.167+15932A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54820 AN: 151888 Hom.: 10566 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.361 AC: 54878 AN: 152006 Hom.: 10580 Cov.: 32 AF XY: 0.368 AC XY: 27313 AN XY: 74302

African (AFR) AF: 0.267 AC: 11068 AN: 41442

American (AMR) AF: 0.517 AC: 7890 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3470

East Asian (EAS) AF: 0.608 AC: 3134 AN: 5156

South Asian (SAS) AF: 0.391 AC: 1885 AN: 4822

European-Finnish (FIN) AF: 0.348 AC: 3682 AN: 10568

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24866 AN: 67970

Other (OTH) AF: 0.388 AC: 818 AN: 2108

Alfa AF: 0.371 Hom.: 45791

Bravo AF: 0.372

Asia WGS AF: 0.505 AC: 1754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.44
PhyloP100		-2.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4379922;

hg19: chr12-125351116;