1-52938539-C-T

Variant names:

• chr1-52938539-C-T
• rs7548389
• NM_002979.5:c.70-3257C>T

Variant summary

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

The NM_002979.5(SCP2):​c.70-3257C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 152,040 control chromosomes in the GnomAD database, including 25,240 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 0.57 (25240 hom., cov: 32)
• Consequence: SCP2 NM_002979.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCP2	NM_002979.5	c.70-3257C>T		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.70-3257C>T		intron_variant	Intron 1 of 15	1	NM_002979.5	ENSP00000360569.3

Frequencies

GnomAD3 genomes AF: 0.566 AC: 86004 AN: 151922 Hom.: 25229 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.0627

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.566 AC: 86054 AN: 152040 Hom.: 25240 Cov.: 32 AF XY: 0.557 AC XY: 41372 AN XY: 74320

African (AFR) AF: 0.608 AC: 25193 AN: 41456

American (AMR) AF: 0.449 AC: 6860 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1923 AN: 3470

East Asian (EAS) AF: 0.0632 AC: 327 AN: 5174

South Asian (SAS) AF: 0.567 AC: 2733 AN: 4820

European-Finnish (FIN) AF: 0.525 AC: 5547 AN: 10560

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41631 AN: 67980

Other (OTH) AF: 0.568 AC: 1199 AN: 2110

Alfa AF: 0.498 Hom.: 1566

Bravo AF: 0.556

Asia WGS AF: 0.307 AC: 1072 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.6
DANN	Benign	0.59
PhyloP100		-0.48
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: rs7548389; hg19: chr1-53404211;