rs7967521

Positions:

• chr12-124832224-T-C
• chr12-124832224-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005505.5(SCARB1):​c.127-14517A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,078 control chromosomes in the GnomAD database, including 19,586 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 0.50 (19586 hom., cov: 33)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCARB1	NM_005505.5	c.127-14517A>G		intron_variant		ENST00000261693.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCARB1	ENST00000261693.11	c.127-14517A>G		intron_variant		1	NM_005505.5	P3

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76085 AN: 151960 Hom.: 19568 Cov.: 33

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.501 AC: 76145 AN: 152078 Hom.: 19586 Cov.: 33 AF XY: 0.499 AC XY: 37123 AN XY: 74326

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.665

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.546

Alfa AF: 0.553 Hom.: 46569

Bravo AF: 0.487

Asia WGS AF: 0.448 AC: 1555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.5
DANN	Benign	0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs7967521; hg19: chr12-125316770;