rs77823283

Positions:

• chr5-170109167-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_012188.5(FOXI1):​c.*556A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 154,204 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (15 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (0 hom.)
• Consequence: FOXI1 NM_012188.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.66

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-170109167-A-G is Benign according to our data. Variant chr5-170109167-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 905481.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXI1	NM_012188.5	c.*556A>G		3_prime_UTR_variant	2/2	ENST00000306268.8
FOXI1	NM_144769.4	c.*556A>G		3_prime_UTR_variant	2/2
FOXI1	XR_941092.2	n.1899A>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXI1	ENST00000306268.8	c.*556A>G		3_prime_UTR_variant	2/2	1	NM_012188.5	P1
FOXI1	ENST00000449804.4	c.*556A>G		3_prime_UTR_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1648 AN: 152152 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.00253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00576

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00436

Gnomad FIN AF: 0.0375

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0147

Gnomad OTH AF: 0.00812

GnomAD4 exome AF: 0.00672 AC: 13 AN: 1934 Hom.: 0 Cov.: 0 AF XY: 0.00818 AC XY: 8 AN XY: 978

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00256

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0122

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00845

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0108 AC: 1647 AN: 152270 Hom.: 15 Cov.: 32 AF XY: 0.0115 AC XY: 856 AN XY: 74448

Gnomad4 AFR AF: 0.00253

Gnomad4 AMR AF: 0.00575

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00436

Gnomad4 FIN AF: 0.0375

Gnomad4 NFE AF: 0.0146

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.0105 Hom.: 1

Bravo AF: 0.00822

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 4 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

May 05, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.22
DANN	Benign	0.78

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: rs77823283; hg19: chr5-169536171;