12-124777293-T-C

Position:

• chr12-124777293-T-C

Variant summary

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

The ENST00000261693.11(SCARB1):​c.*1294A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 152,224 control chromosomes in the GnomAD database, including 65,323 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 0.93 (65320 hom., cov: 32)
  • Exomes 𝑓: 0.75 (3 hom.)
• Consequence: SCARB1 ENST00000261693.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.*1294A>G		3_prime_UTR_variant	13/13	ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.*1294A>G		3_prime_UTR_variant	13/13	1	NM_005505.5	ENSP00000261693	P3

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140829 AN: 152094 Hom.: 65260 Cov.: 32

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.953

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.938

GnomAD4 exome AF: 0.750 AC: 9 AN: 12 Hom.: 3 Cov.: 0 AF XY: 0.750 AC XY: 9 AN XY: 12

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.833

GnomAD4 genome AF: 0.926 AC: 140949 AN: 152212 Hom.: 65320 Cov.: 32 AF XY: 0.922 AC XY: 68559 AN XY: 74386

Gnomad4 AFR AF: 0.934

Gnomad4 AMR AF: 0.953

Gnomad4 ASJ AF: 0.950

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.855

Gnomad4 FIN AF: 0.828

Gnomad4 NFE AF: 0.928

Gnomad4 OTH AF: 0.939

Alfa AF: 0.929 Hom.: 9661

Bravo AF: 0.939

Asia WGS AF: 0.920 AC: 3200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs838883; hg19: chr12-125261839;