1-42262279-T-G

Variant names:

• chr1-42262279-T-G
• rs510157
• NM_014947.5:c.444+2836A>C

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+2836A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,134 control chromosomes in the GnomAD database, including 35,850 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 (35850 hom., cov: 32)
• Consequence: FOXJ3 NM_014947.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.728
• 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.772 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.444+2836A>C		intron	N/A	NP_055762.3
	FOXJ3	NM_001198850.2		c.444+2836A>C		intron	N/A	NP_001185779.1
	FOXJ3	NM_001198851.2		c.444+2836A>C		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.444+2836A>C		intron	N/A	ENSP00000354620.1
	FOXJ3	ENST00000372572.5	TSL:1	c.444+2836A>C		intron	N/A	ENSP00000361653.1
	FOXJ3	ENST00000445886.5	TSL:1	c.444+2836A>C		intron	N/A	ENSP00000393408.1

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102162 AN: 152016 Hom.: 35843 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.672 AC: 102196 AN: 152134 Hom.: 35850 Cov.: 32 AF XY: 0.675 AC XY: 50211 AN XY: 74390

African (AFR) AF: 0.446 AC: 18489 AN: 41492

American (AMR) AF: 0.784 AC: 11982 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2820 AN: 3470

East Asian (EAS) AF: 0.747 AC: 3860 AN: 5168

South Asian (SAS) AF: 0.663 AC: 3189 AN: 4812

European-Finnish (FIN) AF: 0.794 AC: 8422 AN: 10604

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.751 AC: 51055 AN: 67986

Other (OTH) AF: 0.717 AC: 1516 AN: 2114

Alfa AF: 0.729 Hom.: 146367

Bravo AF: 0.666

Asia WGS AF: 0.636 AC: 2214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.7
DANN	Benign	0.70
PhyloP100		0.73
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: rs510157; hg19: chr1-42727950; COSMIC: COSV62360945; COSMIC: COSV62360945;