5-170107104-T-C

Variant names:

• chr5-170107104-T-C
• rs11951903
• NM_012188.5:c.574+573T>C

Variant summary

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

The NM_012188.5(FOXI1):​c.574+573T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 429,976 control chromosomes in the GnomAD database, including 747 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 0.043 (577 hom., cov: 33)
  • Exomes 𝑓: 0.012 (170 hom.)
• Consequence: FOXI1 NM_012188.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.61

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXI1	NM_012188.5	c.574+573T>C		intron_variant	Intron 1 of 1	ENST00000306268.8	NP_036320.2
FOXI1	NM_144769.4	c.574+573T>C		intron_variant	Intron 1 of 1		NP_658982.1
FOXI1	XR_941092.2	n.780+43T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXI1	ENST00000306268.8	c.574+573T>C		intron_variant	Intron 1 of 1	1	NM_012188.5	ENSP00000304286.5
FOXI1	ENST00000449804.4	c.574+573T>C		intron_variant	Intron 1 of 1	1		ENSP00000415483.2

Frequencies

GnomAD3 genomes AF: 0.0433 AC: 6581 AN: 152126 Hom.: 570 Cov.: 33

Gnomad AFR AF: 0.0697

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0300

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.0921

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00666

Gnomad OTH AF: 0.0459

GnomAD4 exome AF: 0.0120 AC: 3343 AN: 277732 Hom.: 170 AF XY: 0.0111 AC XY: 1464 AN XY: 131794

Gnomad4 AFR exome AF: 0.0854

Gnomad4 AMR exome AF: 0.0281

Gnomad4 ASJ exome AF: 0.0182

Gnomad4 EAS exome AF: 0.426

Gnomad4 SAS exome AF: 0.0771

Gnomad4 FIN exome AF: 0.0455

Gnomad4 NFE exome AF: 0.00569

Gnomad4 OTH exome AF: 0.0465

GnomAD4 genome AF: 0.0435 AC: 6615 AN: 152244 Hom.: 577 Cov.: 33 AF XY: 0.0456 AC XY: 3392 AN XY: 74440

Gnomad4 AFR AF: 0.0699

Gnomad4 AMR AF: 0.0301

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.0922

Gnomad4 FIN AF: 0.0120

Gnomad4 NFE AF: 0.00666

Gnomad4 OTH AF: 0.0544

Alfa AF: 0.0268 Hom.: 24

Bravo AF: 0.0463

Asia WGS AF: 0.221 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.027
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11951903; hg19: chr5-169534108;