12-124778515-C-G

Variant names:

• chr12-124778515-C-G
• rs3825140
• NM_005505.5:c.*72G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005505.5(SCARB1):​c.*72G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000185 in 1,079,664 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: SCARB1 NM_005505.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.08
• Publications: 8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.*72G>C		3_prime_UTR_variant	Exon 13 of 13	ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.*72G>C		3_prime_UTR_variant	Exon 13 of 13	1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000185 AC: 2 AN: 1079664 Hom.: 0 Cov.: 32 AF XY: 0.00000192 AC XY: 1 AN XY: 521358

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21500

American (AMR) AF: 0.00 AC: 0 AN: 8054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14056

East Asian (EAS) AF: 0.00 AC: 0 AN: 26084

South Asian (SAS) AF: 0.00 AC: 0 AN: 43774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34428

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3608

European-Non Finnish (NFE) AF: 0.00000226 AC: 2 AN: 885036

Other (OTH) AF: 0.00 AC: 0 AN: 43124

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.14
DANN	Benign	0.40
PhyloP100		-3.1
Mutation Taster		=98/2	polymorphism

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: rs3825140; hg19: chr12-125263061;