rs12747412

Variant names:

• chr1-53037610-C-T
• rs12747412
• NM_002979.5:c.1339-1307C>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.1339-1307C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,654 control chromosomes in the GnomAD database, including 7,289 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 0.27 (7289 hom., cov: 30)
• Consequence: SCP2 NM_002979.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.398 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.1339-1307C>T		intron	N/A	NP_002970.2
	SCP2	NM_001193599.2		c.1267-1307C>T		intron	N/A	NP_001180528.1
	SCP2	NM_001193600.2		c.1207-1307C>T		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.1339-1307C>T		intron	N/A	ENSP00000360569.3
	SCP2	ENST00000371509.8	TSL:1	c.1207-1307C>T		intron	N/A	ENSP00000360564.4
	SCP2	ENST00000435345.6	TSL:1	c.127-1307C>T		intron	N/A	ENSP00000396413.2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41031 AN: 151538 Hom.: 7292 Cov.: 30

Gnomad AFR AF: 0.0690

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.270 AC: 41021 AN: 151654 Hom.: 7289 Cov.: 30 AF XY: 0.263 AC XY: 19473 AN XY: 74088

African (AFR) AF: 0.0689 AC: 2850 AN: 41366

American (AMR) AF: 0.243 AC: 3690 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1252 AN: 3460

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5182

South Asian (SAS) AF: 0.254 AC: 1216 AN: 4792

European-Finnish (FIN) AF: 0.354 AC: 3711 AN: 10470

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27278 AN: 67884

Other (OTH) AF: 0.261 AC: 550 AN: 2104

Alfa AF: 0.355 Hom.: 16311

Bravo AF: 0.251

Asia WGS AF: 0.0990 AC: 344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.44
PhyloP100		-0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97
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: rs12747412; hg19: chr1-53503282;