rs7135223

Variant names:

• chr12-124829868-A-G
• rs7135223
• NM_005505.5:c.127-12161T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-124829868-A-G
• chr12-124829868-A-T

Variant summary

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

The NM_005505.5(SCARB1):​c.127-12161T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,058 control chromosomes in the GnomAD database, including 33,371 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 0.65 (33371 hom., cov: 32)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.127-12161T>C		intron_variant	Intron 1 of 12	ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.127-12161T>C		intron_variant	Intron 1 of 12	1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99493 AN: 151938 Hom.: 33323 Cov.: 32

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.655 AC: 99593 AN: 152058 Hom.: 33371 Cov.: 32 AF XY: 0.653 AC XY: 48544 AN XY: 74346

African (AFR) AF: 0.794 AC: 32955 AN: 41494

American (AMR) AF: 0.673 AC: 10285 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1814 AN: 3470

East Asian (EAS) AF: 0.775 AC: 4020 AN: 5184

South Asian (SAS) AF: 0.579 AC: 2789 AN: 4820

European-Finnish (FIN) AF: 0.582 AC: 6148 AN: 10570

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.583 AC: 39619 AN: 67928

Other (OTH) AF: 0.628 AC: 1326 AN: 2112

Alfa AF: 0.628 Hom.: 9939

Bravo AF: 0.672

Asia WGS AF: 0.667 AC: 2321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.51
PhyloP100		-0.27
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: rs7135223; hg19: chr12-125314414;