1-52949094-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

SCP2 Gene-Disease associations (from GenCC):

• sterol carrier protein 2 deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002979.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCP2	NM_002979.5	MANE Select	c.199+1014T>C		intron	N/A	NP_002970.2
	SCP2	NM_001193599.2		c.128-1661T>C		intron	N/A	NP_001180528.1
	SCP2	NM_001193600.2		c.199+1014T>C		intron	N/A	NP_001180529.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCP2	ENST00000371514.8	TSL:1 MANE Select	c.199+1014T>C		intron	N/A	ENSP00000360569.3
	SCP2	ENST00000371509.8	TSL:1	c.199+1014T>C		intron	N/A	ENSP00000360564.4
	SCP2	ENST00000371513.9	TSL:1	c.199+1014T>C		intron	N/A	ENSP00000360568.5

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

African (AFR) AF: 0.177 AC: 7358 AN: 41516

American (AMR) AF: 0.370 AC: 5650 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1714 AN: 3468

East Asian (EAS) AF: 0.0258 AC: 134 AN: 5194

South Asian (SAS) AF: 0.503 AC: 2423 AN: 4820

European-Finnish (FIN) AF: 0.493 AC: 5193 AN: 10540

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.572 AC: 38848 AN: 67960

Other (OTH) AF: 0.447 AC: 942 AN: 2108

Alfa AF: 0.377 Hom.: 5279

Bravo AF: 0.389

Asia WGS AF: 0.228 AC: 791 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.86
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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