rs483434

Variant names:

• chr17-28523911-A-C
• rs483434
• NM_001369369.1:c.-14-45A>C

Your query was ambiguous. Multiple possible variants found:

• chr17-28523911-A-C
• chr17-28523911-A-G
• chr17-28523911-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.376
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369369.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXN1	NM_001369369.1	MANE Select	c.-14-45A>C		intron	N/A	NP_001356298.1	O15353
	FOXN1	NM_003593.3		c.-59A>C		upstream_gene	N/A	NP_003584.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXN1	ENST00000579795.6	TSL:1 MANE Select	c.-14-45A>C		intron	N/A	ENSP00000464645.1	O15353
	RSKR	ENST00000481916.6	TSL:1	n.*1196-67802T>G		intron	N/A	ENSP00000436369.2	Q96LW2-2
	FOXN1	ENST00000577936.2	TSL:4	c.-9-50A>C		intron	N/A	ENSP00000462159.2	O15353

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139074 AN: 151522 Hom.: 63975 Cov.: 28

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.: 35 AF XY: 0.932 AC XY: 676438 AN XY: 725794

African (AFR) AF: 0.847 AC: 28189 AN: 33282

American (AMR) AF: 0.962 AC: 43021 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.945 AC: 24681 AN: 26122

East Asian (EAS) AF: 0.986 AC: 39125 AN: 39686

South Asian (SAS) AF: 0.824 AC: 70987 AN: 86176

European-Finnish (FIN) AF: 0.975 AC: 51404 AN: 52698

Middle Eastern (MID) AF: 0.903 AC: 5162 AN: 5718

European-Non Finnish (NFE) AF: 0.942 AC: 1045744 AN: 1109952

Other (OTH) AF: 0.929 AC: 56007 AN: 60304

GnomAD4 genome AF: 0.918 AC: 139163 AN: 151640 Hom.: 64010 Cov.: 28 AF XY: 0.919 AC XY: 68108 AN XY: 74114

African (AFR) AF: 0.846 AC: 34836 AN: 41174

American (AMR) AF: 0.955 AC: 14589 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 3266 AN: 3470

East Asian (EAS) AF: 0.976 AC: 4987 AN: 5110

South Asian (SAS) AF: 0.820 AC: 3930 AN: 4794

European-Finnish (FIN) AF: 0.978 AC: 10346 AN: 10580

Middle Eastern (MID) AF: 0.918 AC: 268 AN: 292

European-Non Finnish (NFE) AF: 0.944 AC: 64163 AN: 67934

Other (OTH) AF: 0.906 AC: 1907 AN: 2104

Alfa AF: 0.940 Hom.: 24980

Bravo AF: 0.916

Asia WGS AF: 0.886 AC: 3078 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	13
DANN	Benign	0.49
PhyloP100		0.38
PromoterAI		-0.0018	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs483434; hg19: chr17-26850929;