5-170109541-CT-CTT

Position:

• chr5-170109541-CT-CTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_012188.5(FOXI1):​c.*938dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 151,692 control chromosomes in the GnomAD database, including 7,789 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (7789 hom., cov: 22)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: FOXI1 NM_012188.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.211

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.

• BP6: Variant 5-170109541-C-CT is Benign according to our data. Variant chr5-170109541-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 352722.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXI1	NM_012188.5	c.*938dupT		3_prime_UTR_variant	2/2	ENST00000306268.8	NP_036320.2
FOXI1	NM_144769.4	c.*938dupT		3_prime_UTR_variant	2/2		NP_658982.1
FOXI1	XR_941092.2	n.2281dupT		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXI1	ENST00000306268.8	c.*938dupT		3_prime_UTR_variant	2/2	1	NM_012188.5	ENSP00000304286.5
FOXI1	ENST00000449804.4	c.*938dupT		3_prime_UTR_variant	2/2	1		ENSP00000415483.2

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42510 AN: 151562 Hom.: 7765 Cov.: 22

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.167 AC: 2 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.281 AC: 42583 AN: 151680 Hom.: 7789 Cov.: 22 AF XY: 0.281 AC XY: 20853 AN XY: 74128

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.273

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Nonsyndromic Hearing Loss, Mixed Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3839285; hg19: chr5-169536545;