rs2112669

Positions:

• chr5-170106785-C-G
• chr5-170106785-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012188.5(FOXI1):​c.574+254C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 258,914 control chromosomes in the GnomAD database, including 9,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (8075 hom., cov: 34)
  • Exomes 𝑓: 0.18 (1857 hom.)
• Consequence: FOXI1 NM_012188.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.166

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-170106785-C-G is Benign according to our data. Variant chr5-170106785-C-G is described in ClinVar as [Benign]. Clinvar id is 1237049.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXI1	NM_012188.5	c.574+254C>G		intron_variant		ENST00000306268.8
FOXI1	NM_144769.4	c.574+254C>G		intron_variant
FOXI1	XR_941092.2	n.636-132C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXI1	ENST00000306268.8	c.574+254C>G		intron_variant		1	NM_012188.5	P1
FOXI1	ENST00000449804.4	c.574+254C>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43177 AN: 152116 Hom.: 8050 Cov.: 34

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.177 AC: 18892 AN: 106680 Hom.: 1857 AF XY: 0.177 AC XY: 9020 AN XY: 51028

Gnomad4 AFR exome AF: 0.583

Gnomad4 AMR exome AF: 0.186

Gnomad4 ASJ exome AF: 0.175

Gnomad4 EAS exome AF: 0.457

Gnomad4 SAS exome AF: 0.218

Gnomad4 FIN exome AF: 0.267

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.284 AC: 43251 AN: 152234 Hom.: 8075 Cov.: 34 AF XY: 0.284 AC XY: 21157 AN XY: 74420

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.275

Alfa AF: 0.117 Hom.: 222

Bravo AF: 0.297

Asia WGS AF: 0.339 AC: 1180 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.4
DANN	Benign	0.34

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: rs2112669; hg19: chr5-169533789;