1-10474780-C-G

Variant names:

• chr1-10474780-C-G
• rs115474604
• ENST00000472851.1:n.293+2200C>G

Variant summary

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

The ENST00000472851.1(PEX14):​n.293+2200C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00591 in 651,794 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (98 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (30 hom.)
• Consequence: PEX14 ENST00000472851.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.360

Genes affected

PEX14 (HGNC:8856): (peroxisomal biogenesis factor 14) This gene encodes an essential component of the peroxisomal import machinery. The protein is integrated into peroxisome membranes with its C-terminus exposed to the cytosol, and interacts with the cytosolic receptor for proteins containing a PTS1 peroxisomal targeting signal. The protein also functions as a transcriptional corepressor and interacts with a histone deacetylase. A mutation in this gene results in one form of Zellweger syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 1-10474780-C-G is Benign according to our data. Variant chr1-10474780-C-G is described in ClinVar as [Benign]. Clinvar id is 1226501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX14	NM_004565.3	c.-187C>G		upstream_gene_variant		ENST00000356607.9	NP_004556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX14	ENST00000472851.1	n.293+2200C>G		intron_variant	Intron 1 of 3	3
PEX14	ENST00000356607.9	c.-187C>G		upstream_gene_variant		1	NM_004565.3	ENSP00000349016.4
PEX14	ENST00000491661.2	c.-202C>G		upstream_gene_variant		2		ENSP00000465473.1

Frequencies

GnomAD3 genomes AF: 0.0176 AC: 2683 AN: 152174 Hom.: 98 Cov.: 33

Gnomad AFR AF: 0.0607

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.00233 AC: 1162 AN: 499502 Hom.: 30 AF XY: 0.00186 AC XY: 495 AN XY: 266304

Gnomad4 AFR exome AF: 0.0603

Gnomad4 AMR exome AF: 0.00437

Gnomad4 ASJ exome AF: 0.0000640

Gnomad4 EAS exome AF: 0.0000318

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000229

Gnomad4 OTH exome AF: 0.00466

GnomAD4 genome AF: 0.0176 AC: 2687 AN: 152292 Hom.: 98 Cov.: 33 AF XY: 0.0172 AC XY: 1281 AN XY: 74466

Gnomad4 AFR AF: 0.0606

Gnomad4 AMR AF: 0.00693

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.0200

Asia WGS AF: 0.00318 AC: 11 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 19, 2020

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	-0.76
CADD	Benign	6.9
DANN	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs115474604; hg19: chr1-10534837;