chr17-76137533-C-T

Variant names:

• chr17-76137533-C-T
• rs767689240
• NM_001454.4:c.1086G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001454.4(FOXJ1):​c.1086G>A​(p.Ser362Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000222 in 1,441,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: FOXJ1 NM_001454.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -4.67
• Publications: 0 publications found

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]

FOXJ1 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 43

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 17-76137533-C-T is Benign according to our data. Variant chr17-76137533-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3032647.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-4.67 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 32 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001454.4. 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
	FOXJ1	NM_001454.4	MANE Select	c.1086G>A	p.Ser362Ser	synonymous	Exon 3 of 3	NP_001445.2	Q92949

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXJ1	ENST00000322957.7	TSL:1 MANE Select	c.1086G>A	p.Ser362Ser	synonymous	Exon 3 of 3	ENSP00000323880.4	Q92949
	FOXJ1	ENST00000861552.1		c.1086G>A	p.Ser362Ser	synonymous	Exon 3 of 3	ENSP00000531611.1
	FOXJ1	ENST00000861553.1		c.1086G>A	p.Ser362Ser	synonymous	Exon 2 of 2	ENSP00000531612.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000233 AC: 5 AN: 214340 AF XY: 0.0000172

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000323

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000553

Gnomad NFE exome AF: 0.0000317

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000222 AC: 32 AN: 1441906 Hom.: 0 Cov.: 31 AF XY: 0.0000238 AC XY: 17 AN XY: 715502

African (AFR) AF: 0.00 AC: 0 AN: 33120

American (AMR) AF: 0.0000239 AC: 1 AN: 41902

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25570

East Asian (EAS) AF: 0.00 AC: 0 AN: 38810

South Asian (SAS) AF: 0.00 AC: 0 AN: 83366

European-Finnish (FIN) AF: 0.0000196 AC: 1 AN: 51096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.0000272 AC: 30 AN: 1102722

Other (OTH) AF: 0.00 AC: 0 AN: 59598

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	FOXJ1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.20
DANN	Benign	0.90
PhyloP100		-4.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs767689240; hg19: chr17-74133614;