17-28523911-A-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001369369.1(FOXN1):c.-14-45A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.934 in 1,610,276 control chromosomes in the GnomAD database, including 703,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.92 ( 64010 hom., cov: 28)

Exomes 𝑓: 0.94 ( 639023 hom. )

Consequence

FOXN1
NM_001369369.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.376

Variant links:

Genes affected

FOXN1 (HGNC:12765): (forkhead box N1) Mutations in the winged-helix transcription factor gene at the nude locus in mice and rats produce the pleiotropic phenotype of hairlessness and athymia, resulting in a severely compromised immune system. This gene is orthologous to the mouse and rat genes and encodes a similar DNA-binding transcription factor that is thought to regulate keratin gene expression. A mutation in this gene has been correlated with T-cell immunodeficiency, the skin disorder congenital alopecia, and nail dystrophy. Alternative splicing in the 5' UTR of this gene has been observed. [provided by RefSeq, Jul 2008]

FOXN1 links:

RSKR (HGNC:26314): (ribosomal protein S6 kinase related) Predicted to enable protein kinase activity. Predicted to be involved in protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

RSKR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 17-28523911-A-C is Benign according to our data. Variant chr17-28523911-A-C is described in ClinVar as [Benign]. Clinvar id is 1182314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXN1	NM_001369369.1 link	c.-14-45A>C		intron_variant	Intron 1 of 8	ENST00000579795.6	NP_001356298.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FOXN1	ENST00000579795.6 link	c.-14-45A>C	intron_variant	Intron 1 of 8	1	NM_001369369.1	ENSP00000464645.1	O15353
RSKR	ENST00000481916.6 link	n.*1196-67802T>G	intron_variant	Intron 7 of 7	1		ENSP00000436369.2	Q96LW2-2
FOXN1	ENST00000577936.2 link	c.-9-50A>C	intron_variant	Intron 1 of 8	4		ENSP00000462159.2	O15353J3KRT9
FOXN1	ENST00000226247.2 link	c.-59A>C	upstream_gene_variant		1		ENSP00000226247.2	O15353

Frequencies

GnomAD3 genomes

AF:

0.918

AC:

139074

AN:

151522

Hom.:

63975

Cov.:

show subpopulations

Gnomad AFR

AF:

0.846

Gnomad AMI

AF:

0.957

Gnomad AMR

AF:

0.955

Gnomad ASJ

AF:

0.941

Gnomad EAS

AF:

0.976

Gnomad SAS

AF:

0.820

Gnomad FIN

AF:

0.978

Gnomad MID

AF:

0.920

Gnomad NFE

AF:

0.944

Gnomad OTH

AF:

0.911

GnomAD4 exome

AF:

0.935

AC:

1364320

AN:

1458636

Hom.:

639023

Cov.:

AF XY:

0.932

AC XY:

676438

AN XY:

725794

show subpopulations

Gnomad4 AFR exome

AF:

0.847

Gnomad4 AMR exome

AF:

0.962

Gnomad4 ASJ exome

AF:

0.945

Gnomad4 EAS exome

AF:

0.986

Gnomad4 SAS exome

AF:

0.824

Gnomad4 FIN exome

AF:

0.975

Gnomad4 NFE exome

AF:

0.942

Gnomad4 OTH exome

AF:

0.929

GnomAD4 genome

AF:

0.918

AC:

139163

AN:

151640

Hom.:

64010

Cov.:

AF XY:

0.919

AC XY:

68108

AN XY:

74114

show subpopulations

Gnomad4 AFR

AF:

0.846

Gnomad4 AMR

AF:

0.955

Gnomad4 ASJ

AF:

0.941

Gnomad4 EAS

AF:

0.976

Gnomad4 SAS

AF:

0.820

Gnomad4 FIN

AF:

0.978

Gnomad4 NFE

AF:

0.944

Gnomad4 OTH

AF:

0.906

Alfa

AF:

0.942

Hom.:

19960

Bravo

AF:

0.916

Asia WGS

AF:

0.886

AC:

3078

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 67% of patients studied by a panel of primary immunodeficiencies. Number of patients: 64. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over