rs585320

chr1-42198567-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014947.5(FOXJ3):c.759+535A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,142 control chromosomes in the GnomAD database, including 2,856 homozygotes. 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: 𝑓 0.19 (2856 hom., cov: 32)
• Consequence: FOXJ3 NM_014947.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.594

Genes affected

FOXJ3 (HGNC:29178): (forkhead box J3) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXJ3	NM_014947.5	c.759+535A>G		intron_variant		ENST00000361346.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXJ3	ENST00000361346.6	c.759+535A>G		intron_variant		1	NM_014947.5	P1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29006 AN: 152024 Hom.: 2855 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.164

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.191 AC: 29020 AN: 152142 Hom.: 2856 Cov.: 32 AF XY: 0.191 AC XY: 14233 AN XY: 74372

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.165

Alfa AF: 0.188 Hom.: 2705

Bravo AF: 0.184

Asia WGS AF: 0.257 AC: 893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.6
Dann	Benign	0.58

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

Other links and lift over

dbSNP: rs585320; hg19: chr1-42664238;