1-42243181-T-C

Variant names:

• chr1-42243181-T-C
• rs343389
• NM_014947.5:c.445-15215A>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.445-15215A>G 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 152,058 control chromosomes in the GnomAD database, including 40,985 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 (40985 hom., cov: 31)
• Consequence: FOXJ3 NM_014947.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64
• Publications: 4 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014947.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXJ3	NM_014947.5	MANE Select	c.445-15215A>G		intron	N/A	NP_055762.3
	FOXJ3	NM_001198850.2		c.445-15215A>G		intron	N/A	NP_001185779.1
	FOXJ3	NM_001198851.2		c.445-15215A>G		intron	N/A	NP_001185780.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXJ3	ENST00000361346.6	TSL:1 MANE Select	c.445-15215A>G		intron	N/A	ENSP00000354620.1
	FOXJ3	ENST00000372572.5	TSL:1	c.445-15215A>G		intron	N/A	ENSP00000361653.1
	FOXJ3	ENST00000445886.5	TSL:1	c.445-15215A>G		intron	N/A	ENSP00000393408.1

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111266 AN: 151940 Hom.: 40943 Cov.: 31

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.811

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.752

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: 111368 AN: 152058 Hom.: 40985 Cov.: 31 AF XY: 0.734 AC XY: 54577 AN XY: 74342

African (AFR) AF: 0.656 AC: 27209 AN: 41464

American (AMR) AF: 0.807 AC: 12325 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.811 AC: 2817 AN: 3472

East Asian (EAS) AF: 0.746 AC: 3854 AN: 5168

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

European-Finnish (FIN) AF: 0.795 AC: 8390 AN: 10558

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51114 AN: 67982

Other (OTH) AF: 0.754 AC: 1594 AN: 2114

Alfa AF: 0.677 Hom.: 2422

Bravo AF: 0.735

Asia WGS AF: 0.655 AC: 2281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.86
DANN	Benign	0.27
PhyloP100		-2.6
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: rs343389; hg19: chr1-42708852; COSMIC: COSV62360867;