chr1-52931170-T-G

Variant names:

• chr1-52931170-T-G
• rs1242330
• NM_002979.5:c.69+3705T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002979.5(SCP2):​c.69+3705T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,804 control chromosomes in the GnomAD database, including 15,398 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 (15398 hom., cov: 31)
• Consequence: SCP2 NM_002979.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• Publications: 14 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCP2	NM_002979.5	c.69+3705T>G		intron_variant	Intron 1 of 15	ENST00000371514.8	NP_002970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCP2	ENST00000371514.8	c.69+3705T>G		intron_variant	Intron 1 of 15	1	NM_002979.5	ENSP00000360569.3

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62574 AN: 151684 Hom.: 15407 Cov.: 31

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.412 AC: 62553 AN: 151804 Hom.: 15398 Cov.: 31 AF XY: 0.406 AC XY: 30100 AN XY: 74162

African (AFR) AF: 0.177 AC: 7353 AN: 41490

American (AMR) AF: 0.370 AC: 5650 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1704 AN: 3462

East Asian (EAS) AF: 0.0258 AC: 134 AN: 5184

South Asian (SAS) AF: 0.502 AC: 2417 AN: 4818

European-Finnish (FIN) AF: 0.490 AC: 5140 AN: 10490

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38662 AN: 67796

Other (OTH) AF: 0.445 AC: 939 AN: 2110

Alfa AF: 0.503 Hom.: 60494

Bravo AF: 0.389

Asia WGS AF: 0.230 AC: 801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.74
DANN	Benign	0.51
PhyloP100		-0.064
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: rs1242330; hg19: chr1-53396842; COSMIC: COSV65260702; COSMIC: COSV65260702;