12-124784777-A-T

Variant names:

• chr12-124784777-A-T
• rs838892
• NM_005505.5:c.1401+1580T>A

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.1401+1580T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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.1401+1580T>A		intron	N/A	NP_005496.4
	SCARB1	NM_001367981.1		c.1651+1330T>A		intron	N/A	NP_001354910.1	Q8WTV0-1
	SCARB1	NM_001367983.1		c.1407+1580T>A		intron	N/A	NP_001354912.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	ENST00000261693.11	TSL:1 MANE Select	c.1401+1580T>A		intron	N/A	ENSP00000261693.6	Q8WTV0-2
	SCARB1	ENST00000546215.5	TSL:1	c.1317+1664T>A		intron	N/A	ENSP00000442862.1	B7ZKQ9
	SCARB1	ENST00000535005.5	TSL:1	n.1716+1580T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 202 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 150

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 8

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 178

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.22
PhyloP100		0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs838892; hg19: chr12-125269323;