12-124806460-A-G

Variant names:

• chr12-124806460-A-G
• rs838905
• NM_005505.5:c.1009+1301T>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.1009+1301T>C 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 152,130 control chromosomes in the GnomAD database, including 4,640 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 (4640 hom., cov: 32)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 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.1009+1301T>C		intron	N/A	NP_005496.4
	SCARB1	NM_001367981.1		c.1009+1301T>C		intron	N/A	NP_001354910.1
	SCARB1	NM_001367982.1		c.886+1301T>C		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.1009+1301T>C		intron	N/A	ENSP00000261693.6
	SCARB1	ENST00000546215.5	TSL:1	c.1009+1301T>C		intron	N/A	ENSP00000442862.1
	SCARB1	ENST00000535005.5	TSL:1	n.1324+1301T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27286 AN: 152012 Hom.: 4608 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0508

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0411

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: 27371 AN: 152130 Hom.: 4640 Cov.: 32 AF XY: 0.182 AC XY: 13538 AN XY: 74396

African (AFR) AF: 0.390 AC: 16157 AN: 41460

American (AMR) AF: 0.263 AC: 4020 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0836 AC: 290 AN: 3468

East Asian (EAS) AF: 0.500 AC: 2576 AN: 5154

South Asian (SAS) AF: 0.127 AC: 610 AN: 4820

European-Finnish (FIN) AF: 0.0508 AC: 539 AN: 10614

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0411 AC: 2796 AN: 68016

Other (OTH) AF: 0.157 AC: 332 AN: 2112

Alfa AF: 0.0962 Hom.: 6022

Bravo AF: 0.210

Asia WGS AF: 0.279 AC: 968 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.5
DANN	Benign	0.41
PhyloP100		-0.34
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: rs838905; hg19: chr12-125291006;