12-124863709-G-T

Variant names:

• chr12-124863709-G-T
• rs2070242
• NM_005505.5:c.12C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005505.5(SCARB1):​c.12C>A​(p.Ser4Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,377,306 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. Synonymous variant affecting the same amino acid position (i.e. S4S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: SCARB1 NM_005505.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.396
• Publications: 0 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-0.396 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005505.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	NM_005505.5	MANE Select	c.12C>A	p.Ser4Ser	synonymous	Exon 1 of 13	NP_005496.4
	SCARB1	NM_001367981.1		c.12C>A	p.Ser4Ser	synonymous	Exon 1 of 12	NP_001354910.1
	SCARB1	NM_001367983.1		c.12C>A	p.Ser4Ser	synonymous	Exon 1 of 13	NP_001354912.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	ENST00000261693.11	TSL:1 MANE Select	c.12C>A	p.Ser4Ser	synonymous	Exon 1 of 13	ENSP00000261693.6
	SCARB1	ENST00000546215.5	TSL:1	c.12C>A	p.Ser4Ser	synonymous	Exon 1 of 13	ENSP00000442862.1
	SCARB1	ENST00000535005.5	TSL:1	n.441+3280C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1377306 Hom.: 0 Cov.: 31 AF XY: 0.00000294 AC XY: 2 AN XY: 679982

African (AFR) AF: 0.00 AC: 0 AN: 28268

American (AMR) AF: 0.00 AC: 0 AN: 33860

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24132

East Asian (EAS) AF: 0.00 AC: 0 AN: 33126

South Asian (SAS) AF: 0.00 AC: 0 AN: 77278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5604

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1069750

Other (OTH) AF: 0.00 AC: 0 AN: 56948

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.5
DANN	Benign	0.91
PhyloP100		-0.40
PromoterAI		-0.047	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2070242; hg19: chr12-125348255;