chr1-42250286-C-T

Variant names:

• chr1-42250286-C-T
• rs343386
• NM_014947.5:c.444+14829G>A

Variant summary

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

The NM_014947.5(FOXJ3):​c.444+14829G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 152,058 control chromosomes in the GnomAD database, including 38,033 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 0.70 (38033 hom., cov: 32)
• Consequence: FOXJ3 NM_014947.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXJ3	NM_014947.5	c.444+14829G>A		intron_variant	Intron 4 of 12	ENST00000361346.6	NP_055762.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXJ3	ENST00000361346.6	c.444+14829G>A		intron_variant	Intron 4 of 12	1	NM_014947.5	ENSP00000354620.1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106456 AN: 151940 Hom.: 38018 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.700 AC: 106509 AN: 152058 Hom.: 38033 Cov.: 32 AF XY: 0.703 AC XY: 52221 AN XY: 74330

African (AFR) AF: 0.544 AC: 22525 AN: 41430

American (AMR) AF: 0.796 AC: 12183 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2822 AN: 3470

East Asian (EAS) AF: 0.747 AC: 3863 AN: 5168

South Asian (SAS) AF: 0.664 AC: 3196 AN: 4816

European-Finnish (FIN) AF: 0.795 AC: 8412 AN: 10580

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

European-Non Finnish (NFE) AF: 0.752 AC: 51094 AN: 67976

Other (OTH) AF: 0.732 AC: 1549 AN: 2116

Alfa AF: 0.702 Hom.: 5311

Bravo AF: 0.698

Asia WGS AF: 0.644 AC: 2242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.73
PhyloP100		-0.11
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: rs343386; hg19: chr1-42715957; COSMIC: COSV62360916;