17-76140117-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_001454.4(FOXJ1):​c.279G>A​(p.Ser93Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000855 in 1,590,782 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000094 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000085 ( 1 hom. )

Consequence

FOXJ1
NM_001454.4 synonymous

Scores

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.949
Variant links:
Genes affected
FOXJ1 (HGNC:3816): (forkhead box J1) This gene encodes a member of the forkhead family of transcription factors. Similar genes in zebrafish and mouse have been shown to regulate the transcription of genes that control the production of motile cilia. The mouse ortholog also functions in the determination of left-right asymmetry. Polymorphisms in this gene are associated with systemic lupus erythematosus and allergic rhinitis.[provided by RefSeq, Sep 2009]
RNF157-AS1 (HGNC:44127): (RNF157 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BP6
Variant 17-76140117-C-T is Benign according to our data. Variant chr17-76140117-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3038132.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-0.949 with no splicing effect.
BS2
High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOXJ1NM_001454.4 linkc.279G>A p.Ser93Ser synonymous_variant Exon 2 of 3 ENST00000322957.7 NP_001445.2 Q92949A0A024R8P1
FOXJ1XM_047435666.1 linkc.279G>A p.Ser93Ser synonymous_variant Exon 1 of 2 XP_047291622.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FOXJ1ENST00000322957.7 linkc.279G>A p.Ser93Ser synonymous_variant Exon 2 of 3 1 NM_001454.4 ENSP00000323880.4 Q92949
RNF157-AS1ENST00000662723.1 linkn.89+1597C>T intron_variant Intron 1 of 1

Frequencies

GnomAD3 genomes
AF:
0.0000939
AC:
14
AN:
149066
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000247
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000664
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000164
Gnomad OTH
AF:
0.000494
GnomAD3 exomes
AF:
0.0000842
AC:
18
AN:
213702
Hom.:
0
AF XY:
0.0000930
AC XY:
11
AN XY:
118296
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000309
Gnomad ASJ exome
AF:
0.000214
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000157
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000846
AC:
122
AN:
1441716
Hom.:
1
Cov.:
33
AF XY:
0.0000837
AC XY:
60
AN XY:
717174
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000231
Gnomad4 ASJ exome
AF:
0.000309
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000100
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.0000939
AC:
14
AN:
149066
Hom.:
0
Cov.:
32
AF XY:
0.000124
AC XY:
9
AN XY:
72864
show subpopulations
Gnomad4 AFR
AF:
0.0000247
Gnomad4 AMR
AF:
0.0000664
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000164
Gnomad4 OTH
AF:
0.000494
Alfa
AF:
0.000145
Hom.:
0
Bravo
AF:
0.0000453

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

FOXJ1-related disorder Benign:1
Dec 11, 2023
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.29
CADD
Benign
14
DANN
Benign
0.97

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs375734395; hg19: chr17-74136198; API