1-52949094-T-C

Variant names:

• chr1-52949094-T-C
• rs1242317
• NM_002979.5:c.199+1014T>C

Variant summary

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

The NM_002979.5(SCP2):​c.199+1014T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,068 control chromosomes in the GnomAD database, including 15,551 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 0.41 (15551 hom., cov: 32)
• Consequence: SCP2 NM_002979.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.598

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCP2	NM_002979.5	c.199+1014T>C		intron_variant	Intron 3 of 15	ENST00000371514.8	NP_002970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCP2	ENST00000371514.8	c.199+1014T>C		intron_variant	Intron 3 of 15	1	NM_002979.5	ENSP00000360569.3

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62850 AN: 151950 Hom.: 15561 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.0255

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.413 AC: 62827 AN: 152068 Hom.: 15551 Cov.: 32 AF XY: 0.407 AC XY: 30270 AN XY: 74330

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.0258

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.447

Alfa AF: 0.465 Hom.: 2719

Bravo AF: 0.389

Asia WGS AF: 0.228 AC: 791 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.86

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: rs1242317; hg19: chr1-53414766; COSMIC: COSV65260737;