12-124777047-C-T

Variant names:

• chr12-124777047-C-T
• rs838880
• NM_005505.5:c.*1540G>A

Variant summary

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

The NM_005505.5(SCARB1):​c.*1540G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,888 control chromosomes in the GnomAD database, including 25,173 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 0.55 (25173 hom., cov: 31)
  • Exomes 𝑓: 0.75 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCARB1 NM_005505.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491
• Publications: 92 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.*1540G>A		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.*1540G>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84270 AN: 151770 Hom.: 25174 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.600

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 1 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.555 AC: 84283 AN: 151888 Hom.: 25173 Cov.: 31 AF XY: 0.551 AC XY: 40857 AN XY: 74216

African (AFR) AF: 0.316 AC: 13102 AN: 41406

American (AMR) AF: 0.597 AC: 9116 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2238 AN: 3468

East Asian (EAS) AF: 0.486 AC: 2505 AN: 5154

South Asian (SAS) AF: 0.568 AC: 2733 AN: 4808

European-Finnish (FIN) AF: 0.584 AC: 6130 AN: 10504

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46308 AN: 67974

Other (OTH) AF: 0.595 AC: 1255 AN: 2108

Alfa AF: 0.638 Hom.: 100379

Bravo AF: 0.548

Asia WGS AF: 0.537 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.76
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs838880; hg19: chr12-125261593;