1-52927317-A-T

Variant names:

• chr1-52927317-A-T
• rs115810571
• NM_002979.5:c.-80A>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.-80A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00781 in 1,276,736 control chromosomes in the GnomAD database, including 550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (318 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (232 hom.)
• Consequence: SCP2 NM_002979.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.00
• Publications: 1 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=-0.9).
• BP6: Variant 1-52927317-A-T is Benign according to our data. Variant chr1-52927317-A-T is described in ClinVar as [Benign]. Clinvar id is 1296645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCP2	NM_002979.5	c.-80A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 16	ENST00000371514.8	NP_002970.2
SCP2	NM_002979.5	c.-80A>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.-80A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 16	1	NM_002979.5	ENSP00000360569.3
SCP2	ENST00000371514.8	c.-80A>T		5_prime_UTR_variant	Exon 1 of 16	1	NM_002979.5	ENSP00000360569.3

Frequencies

GnomAD3 genomes AF: 0.0350 AC: 5311 AN: 151818 Hom.: 317 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0127

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000759

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000721

Gnomad OTH AF: 0.0211

GnomAD4 exome AF: 0.00413 AC: 4643 AN: 1124808 Hom.: 232 Cov.: 16 AF XY: 0.00361 AC XY: 2044 AN XY: 566560

African (AFR) AF: 0.127 AC: 3350 AN: 26374

American (AMR) AF: 0.00737 AC: 260 AN: 35272

Ashkenazi Jewish (ASJ) AF: 0.00604 AC: 142 AN: 23504

East Asian (EAS) AF: 0.00 AC: 0 AN: 34546

South Asian (SAS) AF: 0.000298 AC: 22 AN: 73756

European-Finnish (FIN) AF: 0.000507 AC: 21 AN: 41404

Middle Eastern (MID) AF: 0.00587 AC: 21 AN: 3580

European-Non Finnish (NFE) AF: 0.000432 AC: 362 AN: 837210

Other (OTH) AF: 0.00946 AC: 465 AN: 49162

GnomAD4 genome AF: 0.0351 AC: 5326 AN: 151928 Hom.: 318 Cov.: 32 AF XY: 0.0336 AC XY: 2496 AN XY: 74276

African (AFR) AF: 0.121 AC: 4993 AN: 41422

American (AMR) AF: 0.0126 AC: 193 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4812

European-Finnish (FIN) AF: 0.000759 AC: 8 AN: 10542

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000721 AC: 49 AN: 67944

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

Alfa AF: 0.00121 Hom.: 1

Bravo AF: 0.0393

Asia WGS AF: 0.00635 AC: 22 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

- -

Aug 25, 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	-0.90
CADD	Benign	0.29
DANN	Benign	0.37
PhyloP100		-2.0
PromoterAI		0.27	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=300/0	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: rs115810571; hg19: chr1-53392989;