rs77136537

chr5-170107990-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_012188.5(FOXI1):c.575-59G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00973 in 1,347,514 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0098 (18 hom., cov: 33)
  • Exomes 𝑓: 0.0097 (146 hom.)
• Consequence: FOXI1 NM_012188.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.298

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=-0.9).
• BP6: Variant 5-170107990-G-A is Benign according to our data. Variant chr5-170107990-G-A is described in ClinVar as [Benign]. Clinvar id is 1282730.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00976 (1487/152302) while in subpopulation SAS AF= 0.0297 (143/4818). AF 95% confidence interval is 0.0257. There are 18 homozygotes in gnomad4. There are 890 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXI1	NM_012188.5	c.575-59G>A		intron_variant		ENST00000306268.8
FOXI1	NM_144769.4	c.575-344G>A		intron_variant
FOXI1	XR_941092.2	n.781-59G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXI1	ENST00000306268.8	c.575-59G>A		intron_variant		1	NM_012188.5	P1
FOXI1	ENST00000449804.4	c.575-344G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00978 AC: 1488 AN: 152184 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.000820

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.0119

Gnomad SAS AF: 0.0299

Gnomad FIN AF: 0.0444

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00816

Gnomad OTH AF: 0.00526

GnomAD4 exome AF: 0.00972 AC: 11621 AN: 1195212 Hom.: 146 AF XY: 0.0103 AC XY: 6239 AN XY: 607794

Gnomad4 AFR exome AF: 0.000672

Gnomad4 AMR exome AF: 0.0175

Gnomad4 ASJ exome AF: 0.00944

Gnomad4 EAS exome AF: 0.0113

Gnomad4 SAS exome AF: 0.0260

Gnomad4 FIN exome AF: 0.0471

Gnomad4 NFE exome AF: 0.00588

Gnomad4 OTH exome AF: 0.00882

GnomAD4 genome AF: 0.00976 AC: 1487 AN: 152302 Hom.: 18 Cov.: 33 AF XY: 0.0120 AC XY: 890 AN XY: 74472

Gnomad4 AFR AF: 0.000818

Gnomad4 AMR AF: 0.0111

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.0120

Gnomad4 SAS AF: 0.0297

Gnomad4 FIN AF: 0.0444

Gnomad4 NFE AF: 0.00816

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.0144 Hom.: 3

Bravo AF: 0.00595

Asia WGS AF: 0.0220 AC: 76 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

Jan 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.84
Dann	Benign	0.48

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: rs77136537; hg19: chr5-169534994; COSMIC: COSV60389644;