1-42274121-G-T

Variant names:

• chr1-42274121-G-T
• rs4660616
• NM_014947.5:c.369+4227C>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.369+4227C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,060 control chromosomes in the GnomAD database, including 44,091 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 0.76 (44091 hom., cov: 31)
• Consequence: FOXJ3 NM_014947.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273
• Publications: 2 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.803 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXJ3	NM_014947.5	MANE Select	c.369+4227C>A		intron	N/A	NP_055762.3
	FOXJ3	NM_001198850.2		c.369+4227C>A		intron	N/A	NP_001185779.1	Q9UPW0-1
	FOXJ3	NM_001198851.2		c.369+4227C>A		intron	N/A	NP_001185780.1	Q9UPW0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXJ3	ENST00000361346.6	TSL:1 MANE Select	c.369+4227C>A		intron	N/A	ENSP00000354620.1	Q9UPW0-1
	FOXJ3	ENST00000372572.5	TSL:1	c.369+4227C>A		intron	N/A	ENSP00000361653.1	Q9UPW0-1
	FOXJ3	ENST00000445886.5	TSL:1	c.369+4227C>A		intron	N/A	ENSP00000393408.1	C9JVP0

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115615 AN: 151942 Hom.: 44046 Cov.: 31

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.761 AC: 115722 AN: 152060 Hom.: 44091 Cov.: 31 AF XY: 0.762 AC XY: 56611 AN XY: 74318

African (AFR) AF: 0.756 AC: 31326 AN: 41452

American (AMR) AF: 0.815 AC: 12463 AN: 15288

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

East Asian (EAS) AF: 0.747 AC: 3845 AN: 5146

South Asian (SAS) AF: 0.665 AC: 3204 AN: 4818

European-Finnish (FIN) AF: 0.795 AC: 8399 AN: 10570

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51153 AN: 68002

Other (OTH) AF: 0.777 AC: 1639 AN: 2110

Alfa AF: 0.758 Hom.: 6374

Bravo AF: 0.766

Asia WGS AF: 0.661 AC: 2300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.3
DANN	Benign	0.43
PhyloP100		0.27
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: rs4660616; hg19: chr1-42739792; COSMIC: COSV62360999;