Genetic Variant ENST00000345097.8:c.-15+41991G>T (chr14-89577037-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000345097.8(FOXN3):c.-15+41991G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 152,168 control chromosomes in the GnomAD database, including 60,764 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 0.89 ( 60763 hom., cov: 32)

Exomes 𝑓: 1.0 ( 1 hom. )

Consequence

FOXN3
ENST00000345097.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.236

Publications

5 publications found

Variant links:

Genes affected

FOXN3 (HGNC:1928): (forkhead box N3) This gene is a member of the forkhead/winged helix transcription factor family. Checkpoints are eukaryotic DNA damage-inducible cell cycle arrests at G1 and G2. Checkpoint suppressor 1 suppresses multiple yeast checkpoint mutations including mec1, rad9, rad53 and dun1 by activating a MEC1-independent checkpoint pathway. Alternative splicing is observed at the locus, resulting in distinct isoforms. [provided by RefSeq, Jul 2008]

FOXN3 links:

FOXN3-AS2 (HGNC:30119): (FOXN3 antisense RNA 2)

FOXN3-AS2 links:

ENSG00000259053 (HGNC:):

ENSG00000259053 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXN3-AS2	NR_024620.1 link	n.822C>A		non_coding_transcript_exon_variant	Exon 1 of 1
FOXN3	NM_001085471.2 link	c.-15+41991G>T		intron_variant	Intron 1 of 6		NP_001078940.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
FOXN3	ENST00000345097.8 link	c.-15+41991G>T	intron_variant	Intron 1 of 6	1	ENSP00000343288.4
FOXN3	ENST00000555353.5 link	c.-15+41991G>T	intron_variant	Intron 1 of 5	1	ENSP00000452227.1
FOXN3-AS2	ENST00000554071.1 link	n.822C>A	non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.891

AC:

135469

AN:

152048

Hom.:

60710

Cov.:

show subpopulations

Gnomad AFR

AF:

0.938

Gnomad AMI

AF:

0.813

Gnomad AMR

AF:

0.915

Gnomad ASJ

AF:

0.778

Gnomad EAS

AF:

0.627

Gnomad SAS

AF:

0.766

Gnomad FIN

AF:

0.906

Gnomad MID

AF:

0.835

Gnomad NFE

AF:

0.891

Gnomad OTH

AF:

0.883

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.891

AC:

135574

AN:

152166

Hom.:

60763

Cov.:

AF XY:

0.888

AC XY:

66079

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.938

AC:

38960

AN:

41528

American (AMR)

AF:

0.915

AC:

13986

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.778

AC:

2700

AN:

3470

East Asian (EAS)

AF:

0.627

AC:

3235

AN:

5156

South Asian (SAS)

AF:

0.765

AC:

3685

AN:

4814

European-Finnish (FIN)

AF:

0.906

AC:

9595

AN:

10588

Middle Eastern (MID)

AF:

0.837

AC:

246

AN:

294

European-Non Finnish (NFE)

AF:

0.891

AC:

60590

AN:

68012

Other (OTH)

AF:

0.872

AC:

1839

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

725

1451

2176

2902

3627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.883

Hom.:

107729

Bravo

AF:

0.894

Asia WGS

AF:

0.667

AC:

2323

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

1.5

(source)

DANN

Benign

0.79

PhyloP100

-0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over