rs2282404

Positions:

• chr1-42335634-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000436207.2(ENSG00000227527):​n.452-39G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 151,916 control chromosomes in the GnomAD database, including 183 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 0.014 (183 hom., cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENST00000436207.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.497

Genes affected

(HGNC:):

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXJ3	NM_001198850.2	c.-26G>A		5_prime_UTR_variant	1/13
FOXJ3	XM_024454163.2	c.-170G>A		5_prime_UTR_variant	1/14
FOXJ3	XM_047449488.1	c.-26G>A		5_prime_UTR_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000436207.2	n.452-39G>A		intron_variant, non_coding_transcript_variant		5
FOXJ3	ENST00000372573.5	c.-26G>A		5_prime_UTR_variant	1/13	2		P1

Frequencies

GnomAD3 genomes AF: 0.0139 AC: 2114 AN: 151796 Hom.: 184 Cov.: 29

Gnomad AFR AF: 0.00167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0250

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.0201

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00165

Gnomad OTH AF: 0.0139

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 112 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 74

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0139 AC: 2117 AN: 151916 Hom.: 183 Cov.: 29 AF XY: 0.0152 AC XY: 1132 AN XY: 74244

Gnomad4 AFR AF: 0.00166

Gnomad4 AMR AF: 0.0252

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.00977

Gnomad4 FIN AF: 0.0201

Gnomad4 NFE AF: 0.00165

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00964 Hom.: 4

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.3
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2282404; hg19: chr1-42801305;