X-130656575-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006375.4(ENOX2):​c.1129+6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,032,789 control chromosomes in the GnomAD database, including 72 homozygotes. There are 3,574 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0087 ( 4 hom., 249 hem., cov: 24)
Exomes 𝑓: 0.013 ( 68 hom. 3325 hem. )

Consequence

ENOX2
NM_006375.4 splice_region, intron

Scores

2
Splicing: ADA: 0.0004812
2

Clinical Significance

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

Conservation

PhyloP100: -0.439
Variant links:
Genes affected
ENOX2 (HGNC:2259): (ecto-NOX disulfide-thiol exchanger 2) This gene is a tumor-specific member of the ECTO-NOX family of genes that encode cell surface NADH oxidases. The encoded protein has two enzymatic activities: catalysis of hydroquinone or NADH oxidation, and protein disulfide interchange. The protein also displays prion-like properties. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant X-130656575-C-T is Benign according to our data. Variant chrX-130656575-C-T is described in ClinVar as [Benign]. Clinvar id is 789254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-130656575-C-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0129 (11875/920381) while in subpopulation NFE AF= 0.0159 (10899/685912). AF 95% confidence interval is 0.0156. There are 68 homozygotes in gnomad4_exome. There are 3325 alleles in male gnomad4_exome subpopulation. Median coverage is 16. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ENOX2NM_006375.4 linkc.1129+6G>A splice_region_variant, intron_variant Intron 10 of 14 ENST00000394363.6 NP_006366.2 Q16206-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENOX2ENST00000394363.6 linkc.1129+6G>A splice_region_variant, intron_variant Intron 10 of 14 2 NM_006375.4 ENSP00000377890.1 Q16206-2

Frequencies

GnomAD3 genomes
AF:
0.00874
AC:
982
AN:
112356
Hom.:
4
Cov.:
24
AF XY:
0.00724
AC XY:
250
AN XY:
34520
show subpopulations
Gnomad AFR
AF:
0.00191
Gnomad AMI
AF:
0.00439
Gnomad AMR
AF:
0.00816
Gnomad ASJ
AF:
0.00414
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00112
Gnomad FIN
AF:
0.00262
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0148
Gnomad OTH
AF:
0.00933
GnomAD3 exomes
AF:
0.00840
AC:
1427
AN:
169902
Hom.:
2
AF XY:
0.00855
AC XY:
492
AN XY:
57548
show subpopulations
Gnomad AFR exome
AF:
0.00126
Gnomad AMR exome
AF:
0.00615
Gnomad ASJ exome
AF:
0.00512
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00210
Gnomad FIN exome
AF:
0.00350
Gnomad NFE exome
AF:
0.0143
Gnomad OTH exome
AF:
0.00745
GnomAD4 exome
AF:
0.0129
AC:
11875
AN:
920381
Hom.:
68
Cov.:
16
AF XY:
0.0125
AC XY:
3325
AN XY:
265109
show subpopulations
Gnomad4 AFR exome
AF:
0.00159
Gnomad4 AMR exome
AF:
0.00568
Gnomad4 ASJ exome
AF:
0.00664
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00269
Gnomad4 FIN exome
AF:
0.00307
Gnomad4 NFE exome
AF:
0.0159
Gnomad4 OTH exome
AF:
0.00920
GnomAD4 genome
AF:
0.00872
AC:
980
AN:
112408
Hom.:
4
Cov.:
24
AF XY:
0.00720
AC XY:
249
AN XY:
34582
show subpopulations
Gnomad4 AFR
AF:
0.00190
Gnomad4 AMR
AF:
0.00815
Gnomad4 ASJ
AF:
0.00414
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00112
Gnomad4 FIN
AF:
0.00262
Gnomad4 NFE
AF:
0.0148
Gnomad4 OTH
AF:
0.00921
Alfa
AF:
0.0105
Hom.:
80
Bravo
AF:
0.00800

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

- -

Apr 03, 2018
Labcorp Genetics (formerly Invitae), Labcorp
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
-0.74
CADD
Benign
13
DANN
Benign
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00048
dbscSNV1_RF
Benign
0.084
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

Publications

LitVar

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

Other links and lift over

dbSNP: rs147492521; hg19: chrX-129790549; API