rs1125792

Variant names:

• chr1-42283662-C-A
• rs1125792
• NM_014947.5:c.45-4990G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014947.5(FOXJ3):​c.45-4990G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 152,042 control chromosomes in the GnomAD database, including 40,981 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 0.73 (40981 hom., cov: 31)
• Consequence: FOXJ3 NM_014947.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXJ3	NM_014947.5	c.45-4990G>T		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.45-4990G>T		intron_variant	Intron 2 of 12	1	NM_014947.5	ENSP00000354620.1

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111260 AN: 151924 Hom.: 40940 Cov.: 31

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.710

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.755

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

GnomAD4 genome AF: 0.732 AC: 111361 AN: 152042 Hom.: 40981 Cov.: 31 AF XY: 0.734 AC XY: 54576 AN XY: 74324

African (AFR) AF: 0.657 AC: 27220 AN: 41458

American (AMR) AF: 0.806 AC: 12315 AN: 15274

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

East Asian (EAS) AF: 0.746 AC: 3861 AN: 5174

South Asian (SAS) AF: 0.665 AC: 3201 AN: 4812

European-Finnish (FIN) AF: 0.795 AC: 8415 AN: 10582

Middle Eastern (MID) AF: 0.712 AC: 208 AN: 292

European-Non Finnish (NFE) AF: 0.751 AC: 51073 AN: 67964

Other (OTH) AF: 0.754 AC: 1588 AN: 2106

Alfa AF: 0.740 Hom.: 12243

Bravo AF: 0.735

Asia WGS AF: 0.657 AC: 2288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.3
DANN	Benign	0.46
PhyloP100		-1.5
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: rs1125792; hg19: chr1-42749333; COSMIC: COSV62361051;