1-52927340-C-T

Position:

• chr1-52927340-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002979.5(SCP2):​c.-57C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,438,006 control chromosomes in the GnomAD database, including 371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (195 hom., cov: 32)
  • Exomes 𝑓: 0.0095 (176 hom.)
• Consequence: SCP2 NM_002979.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.551

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-52927340-C-T is Benign according to our data. Variant chr1-52927340-C-T is described in ClinVar as [Benign]. Clinvar id is 1227815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.087 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCP2	NM_002979.5	c.-57C>T		5_prime_UTR_variant	1/16	ENST00000371514.8	NP_002970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCP2	ENST00000371514.8	c.-57C>T		5_prime_UTR_variant	1/16	1	NM_002979.5	ENSP00000360569	P1

Frequencies

GnomAD3 genomes AF: 0.0296 AC: 4507 AN: 152186 Hom.: 195 Cov.: 32

Gnomad AFR AF: 0.0894

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00758

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.00945 AC: 12155 AN: 1285702 Hom.: 176 Cov.: 19 AF XY: 0.00902 AC XY: 5771 AN XY: 640084

Gnomad4 AFR exome AF: 0.0906

Gnomad4 AMR exome AF: 0.00667

Gnomad4 ASJ exome AF: 0.00478

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00226

Gnomad4 FIN exome AF: 0.00477

Gnomad4 NFE exome AF: 0.00837

Gnomad4 OTH exome AF: 0.00940

GnomAD4 genome AF: 0.0297 AC: 4516 AN: 152304 Hom.: 195 Cov.: 32 AF XY: 0.0276 AC XY: 2055 AN XY: 74480

Gnomad4 AFR AF: 0.0894

Gnomad4 AMR AF: 0.0114

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00499

Gnomad4 NFE AF: 0.00759

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0197 Hom.: 12

Bravo AF: 0.0327

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.7
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs140752743; hg19: chr1-53393012;