1-10474780-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.360
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
PEX14NM_004565.3 linkc.-187C>G upstream_gene_variant ENST00000356607.9 NP_004556.1 O75381-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PEX14ENST00000472851.1 linkn.293+2200C>G intron_variant Intron 1 of 3 3
PEX14ENST00000356607.9 linkc.-187C>G upstream_gene_variant 1 NM_004565.3 ENSP00000349016.4 O75381-1
PEX14ENST00000491661.2 linkc.-202C>G upstream_gene_variant 2 ENSP00000465473.1 K7EK59

Frequencies

GnomAD3 genomes
AF:
0.0176
AC:
2683
AN:
152174
Hom.:
98
Cov.:
33
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs115474604; hg19: chr1-10534837; API