NM_014947.5:c.45-12814A>G

Variant names:

• chr1-42291486-T-C
• rs7539485
• NM_014947.5:c.45-12814A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FOXJ3	NM_014947.5	c.45-12814A>G		intron_variant	Intron 2 of 12	ENST00000361346.6	NP_055762.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXJ3	ENST00000361346.6	c.45-12814A>G		intron_variant	Intron 2 of 12	1	NM_014947.5	ENSP00000354620.1

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

African (AFR) AF: 0.431 AC: 17858 AN: 41426

American (AMR) AF: 0.784 AC: 11987 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2822 AN: 3472

East Asian (EAS) AF: 0.744 AC: 3838 AN: 5162

South Asian (SAS) AF: 0.664 AC: 3202 AN: 4820

European-Finnish (FIN) AF: 0.795 AC: 8391 AN: 10560

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.751 AC: 51049 AN: 67958

Other (OTH) AF: 0.713 AC: 1500 AN: 2104

Alfa AF: 0.727 Hom.: 20633

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
PhyloP100		0.035
Mutation Taster		=100/0	polymorphism (auto)

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