1-52927340-C-T

Variant names:

• chr1-52927340-C-T
• rs140752743
• NM_002979.5:c.-57C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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]

ECHDC2 (HGNC:23408): (enoyl-CoA hydratase domain containing 2) Predicted to enable enoyl-CoA hydratase activity. Predicted to be involved in fatty acid beta-oxidation. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SCP2	NM_002979.5	c.-57C>T		5_prime_UTR_variant	Exon 1 of 16	ENST00000371514.8	NP_002970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCP2	ENST00000371514.8	c.-57C>T		5_prime_UTR_variant	Exon 1 of 16	1	NM_002979.5	ENSP00000360569.3

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

African (AFR) AF: 0.0906 AC: 2683 AN: 29628

American (AMR) AF: 0.00667 AC: 238 AN: 35676

Ashkenazi Jewish (ASJ) AF: 0.00478 AC: 117 AN: 24480

East Asian (EAS) AF: 0.00 AC: 0 AN: 35752

South Asian (SAS) AF: 0.00226 AC: 174 AN: 77158

European-Finnish (FIN) AF: 0.00477 AC: 219 AN: 45932

Middle Eastern (MID) AF: 0.00558 AC: 22 AN: 3944

European-Non Finnish (NFE) AF: 0.00837 AC: 8192 AN: 978852

Other (OTH) AF: 0.00940 AC: 510 AN: 54280

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

African (AFR) AF: 0.0894 AC: 3714 AN: 41558

American (AMR) AF: 0.0114 AC: 175 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4826

European-Finnish (FIN) AF: 0.00499 AC: 53 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00759 AC: 516 AN: 68028

Other (OTH) AF: 0.0147 AC: 31 AN: 2114

Alfa AF: 0.0212 Hom.: 16

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.7
DANN	Benign	0.81
PhyloP100		-0.55
PromoterAI		-0.00050	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=297/3	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: rs140752743; hg19: chr1-53393012;