chr17-28523910-CA-C

Position:

• chr17-28523910-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001369369.1(FOXN1):​c.-14-45del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000514 in 1,610,168 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 28)
  • Exomes 𝑓: 0.00029 (4 hom.)
• Consequence: FOXN1 NM_001369369.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.376

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]

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-28523910-CA-C is Benign according to our data. Variant chr17-28523910-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1216140.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00269 (409/151884) while in subpopulation AFR AF= 0.00926 (383/41372). AF 95% confidence interval is 0.00849. There are 1 homozygotes in gnomad4. There are 163 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 4 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXN1	NM_001369369.1	c.-14-45del		intron_variant		ENST00000579795.6	NP_001356298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXN1	ENST00000579795.6	c.-14-45del		intron_variant		1	NM_001369369.1	ENSP00000464645	P1
RSKR	ENST00000481916.6	c.*1196-67802del		intron_variant, NMD_transcript_variant		1		ENSP00000436369
FOXN1	ENST00000577936.2	c.-9-50del		intron_variant		4		ENSP00000462159	P1
FOXN1	ENST00000226247.2			upstream_gene_variant		1		ENSP00000226247	P1

Frequencies

GnomAD3 genomes AF: 0.00269 AC: 409 AN: 151768 Hom.: 1 Cov.: 28

Gnomad AFR AF: 0.00928

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00112

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00241

GnomAD4 exome AF: 0.000287 AC: 419 AN: 1458284 Hom.: 4 Cov.: 35 AF XY: 0.000249 AC XY: 181 AN XY: 725682

Gnomad4 AFR exome AF: 0.00999

Gnomad4 AMR exome AF: 0.000514

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000207

Gnomad4 OTH exome AF: 0.000498

GnomAD4 genome AF: 0.00269 AC: 409 AN: 151884 Hom.: 1 Cov.: 28 AF XY: 0.00220 AC XY: 163 AN XY: 74240

Gnomad4 AFR AF: 0.00926

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000589

Gnomad4 OTH AF: 0.00238

Bravo AF: 0.00304

Asia WGS AF: 0.000867 AC: 3 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 27, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs573288127; hg19: chr17-26850928;