rs7380481

Positions:

• chr5-170107541-T-C

Variant summary

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

The NM_012188.5(FOXI1):​c.575-508T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,112 control chromosomes in the GnomAD database, including 6,414 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 0.28 (6414 hom., cov: 32)
• Consequence: FOXI1 NM_012188.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272

Genes affected

FOXI1 (HGNC:3815): (forkhead box I1) This gene belongs to the forkhead family of transcription factors, which is characterized by a distinct forkhead domain. This gene may play an important role in the development of the cochlea and vestibulum, as well as in embryogenesis. The encoded protein has been found to be required for the transcription of four subunits of a proton pump found in the inner ear, the kidney, and the epididymis. Mutations in this gene have been associated with deafness, autosomal recessive 4. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXI1	NM_012188.5	c.575-508T>C		intron_variant		ENST00000306268.8	NP_036320.2
FOXI1	NM_144769.4	c.575-793T>C		intron_variant			NP_658982.1
FOXI1	XR_941092.2	n.780+480T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXI1	ENST00000306268.8	c.575-508T>C		intron_variant		1	NM_012188.5	ENSP00000304286	P1
FOXI1	ENST00000449804.4	c.575-793T>C		intron_variant		1		ENSP00000415483

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42087 AN: 151994 Hom.: 6420 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.266

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.277 AC: 42072 AN: 152112 Hom.: 6414 Cov.: 32 AF XY: 0.276 AC XY: 20524 AN XY: 74386

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.263

Alfa AF: 0.302 Hom.: 913

Bravo AF: 0.276

Asia WGS AF: 0.285 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.8
DANN	Benign	0.39

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: rs7380481; hg19: chr5-169534545;