1-42291486-T-C

Position:

• chr1-42291486-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.45-12814A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 151,988 control chromosomes in the GnomAD database, including 35,586 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 0.67 (35586 hom., cov: 31)
• Consequence: FOXJ3 NM_014947.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXJ3	NM_014947.5	c.45-12814A>G		intron_variant		ENST00000361346.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXJ3	ENST00000361346.6	c.45-12814A>G		intron_variant		1	NM_014947.5	P1

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101478 AN: 151870 Hom.: 35579 Cov.: 31

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.668 AC: 101512 AN: 151988 Hom.: 35586 Cov.: 31 AF XY: 0.671 AC XY: 49868 AN XY: 74288

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.813

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.751

Gnomad4 OTH AF: 0.713

Alfa AF: 0.727 Hom.: 18385

Bravo AF: 0.661

Asia WGS AF: 0.632 AC: 2200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.5
DANN	Benign	0.85

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: rs7539485; hg19: chr1-42757157; COSMIC: COSV62361082;