chr1-52990227-T-C

Variant names:

• chr1-52990227-T-C
• rs11206061
• NM_002979.5:c.1081+2091T>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.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
• 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=-0.95).
• 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 rank	MANE	Protein	UniProt
SCP2	NM_002979.5	c.1081+2091T>C		intron_variant	Intron 11 of 15	ENST00000371514.8	NP_002970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCP2	ENST00000371514.8	c.1081+2091T>C		intron_variant	Intron 11 of 15	1	NM_002979.5	ENSP00000360569.3

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

African (AFR) AF: 0.459 AC: 18955 AN: 41294

American (AMR) AF: 0.0941 AC: 1436 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0517 AC: 179 AN: 3464

East Asian (EAS) AF: 0.0421 AC: 217 AN: 5160

South Asian (SAS) AF: 0.0848 AC: 407 AN: 4802

European-Finnish (FIN) AF: 0.0267 AC: 283 AN: 10584

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0471 AC: 3198 AN: 67962

Other (OTH) AF: 0.153 AC: 323 AN: 2110

Alfa AF: 0.0941 Hom.: 3640

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
PhyloP100		1.1
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: rs11206061; hg19: chr1-53455899;