rs2068485660

Variant names:

• chr17-76137358-A-G
• rs2068485660
• NM_001454.4:c.1261T>C
• FOXJ1 p.Leu421Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001454.4(FOXJ1):​c.1261T>C​(p.Leu421Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000075 in 1,333,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: FOXJ1 NM_001454.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• 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: Ambry Genetics, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=1.18 with no splicing effect.

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.1261T>C	p.Leu421Leu	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.1261T>C	p.Leu421Leu	synonymous	Exon 3 of 3	ENSP00000323880.4	Q92949
	FOXJ1	ENST00000861552.1		c.1261T>C	p.Leu421Leu	synonymous	Exon 3 of 3	ENSP00000531611.1
	FOXJ1	ENST00000861553.1		c.1261T>C	p.Leu421Leu	synonymous	Exon 2 of 2	ENSP00000531612.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.50e-7 AC: 1 AN: 1333650 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 652304

African (AFR) AF: 0.00 AC: 0 AN: 30352

American (AMR) AF: 0.00 AC: 0 AN: 30358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21692

East Asian (EAS) AF: 0.00 AC: 0 AN: 35242

South Asian (SAS) AF: 0.00 AC: 0 AN: 71698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4064

European-Non Finnish (NFE) AF: 9.51e-7 AC: 1 AN: 1051974

Other (OTH) AF: 0.00 AC: 0 AN: 55484

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.0
DANN	Benign	0.75
PhyloP100		1.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2068485660;

hg19: chr17-74133439;