1-10474780-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

PEX14 Gene-Disease associations (from GenCC):

• peroxisome biogenesis disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• peroxisome biogenesis disorder 13A (Zellweger)

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• Zellweger spectrum disorders

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000472851.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX14	NM_004565.3	MANE Select	c.-187C>G		upstream_gene	N/A	NP_004556.1	O75381-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX14	ENST00000472851.1	TSL:3	n.293+2200C>G		intron	N/A
	PEX14	ENST00000356607.9	TSL:1 MANE Select	c.-187C>G		upstream_gene	N/A	ENSP00000349016.4	O75381-1
	PEX14	ENST00000889280.1		c.-187C>G		upstream_gene	N/A	ENSP00000559339.1

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

African (AFR) AF: 0.0603 AC: 834 AN: 13824

American (AMR) AF: 0.00437 AC: 108 AN: 24732

Ashkenazi Jewish (ASJ) AF: 0.0000640 AC: 1 AN: 15616

East Asian (EAS) AF: 0.0000318 AC: 1 AN: 31414

South Asian (SAS) AF: 0.00 AC: 0 AN: 52132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41818

Middle Eastern (MID) AF: 0.00623 AC: 23 AN: 3692

European-Non Finnish (NFE) AF: 0.000229 AC: 66 AN: 288562

Other (OTH) AF: 0.00466 AC: 129 AN: 27712

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

African (AFR) AF: 0.0606 AC: 2518 AN: 41558

American (AMR) AF: 0.00693 AC: 106 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68030

Other (OTH) AF: 0.0156 AC: 33 AN: 2112

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.0200

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.9
DANN	Benign	0.78
PhyloP100		-0.36
PromoterAI		-0.10	Neutral

Splicing

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

Other links and lift over

dbSNP: rs115474604; hg19: chr1-10534837;