chr1-52990227-T-C

Position:

• chr1-52990227-T-C

Variant summary

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

The NM_002979.5(SCP2):​c.1081+2091T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 151,838 control chromosomes in the GnomAD database, including 4,566 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 0.17 (4566 hom., cov: 31)
• Consequence: SCP2 NM_002979.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

Genes affected

SCP2 (HGNC:10606): (sterol carrier protein 2) This gene encodes two proteins: sterol carrier protein X (SCPx) and sterol carrier protein 2 (SCP2), as a result of transcription initiation from 2 independently regulated promoters. The transcript initiated from the proximal promoter encodes the longer SCPx protein, and the transcript initiated from the distal promoter encodes the shorter SCP2 protein, with the 2 proteins sharing a common C-terminus. Evidence suggests that the SCPx protein is a peroxisome-associated thiolase that is involved in the oxidation of branched chain fatty acids, while the SCP2 protein is thought to be an intracellular lipid transfer protein. This gene is highly expressed in organs involved in lipid metabolism, and may play a role in Zellweger syndrome, in which cells are deficient in peroxisomes and have impaired bile acid synthesis. Alternative splicing of this gene produces multiple transcript variants, some encoding different isoforms.[provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCP2	NM_002979.5	c.1081+2091T>C		intron_variant		ENST00000371514.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCP2	ENST00000371514.8	c.1081+2091T>C		intron_variant		1	NM_002979.5	P1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25007 AN: 151720 Hom.: 4551 Cov.: 31

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0943

Gnomad ASJ AF: 0.0517

Gnomad EAS AF: 0.0420

Gnomad SAS AF: 0.0853

Gnomad FIN AF: 0.0267

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0471

Gnomad OTH AF: 0.155

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.165 AC: 25059 AN: 151838 Hom.: 4566 Cov.: 31 AF XY: 0.162 AC XY: 12033 AN XY: 74200

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.0941

Gnomad4 ASJ AF: 0.0517

Gnomad4 EAS AF: 0.0421

Gnomad4 SAS AF: 0.0848

Gnomad4 FIN AF: 0.0267

Gnomad4 NFE AF: 0.0471

Gnomad4 OTH AF: 0.153

Alfa AF: 0.0819 Hom.: 696

Bravo AF: 0.181

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	7.5
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs11206061; hg19: chr1-53455899;