Variant rs77136537 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.298

Variant links:

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]

FOXI1 links:

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ACMG classification

Classification made for transcript

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. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
FOXI1	NM_012188.5 linkuse as main transcript	c.575-59G>A	intron_variant	ENST00000306268.8	NP_036320.2
FOXI1	NM_144769.4 linkuse as main transcript	c.575-344G>A	intron_variant		NP_658982.1
FOXI1	XR_941092.2 linkuse as main transcript	n.781-59G>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXI1	ENST00000306268.8 linkuse as main transcript	c.575-59G>A		intron_variant		1	NM_012188.5	ENSP00000304286	P1	Q12951-1
FOXI1	ENST00000449804.4 linkuse as main transcript	c.575-344G>A		intron_variant		1		ENSP00000415483		Q12951-2

Frequencies

GnomAD3 genomes

AF:

0.00978

AC:

1488

AN:

152184

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.0120

AC XY:

890

AN XY:

74472

show subpopulations

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.:

Bravo

AF:

0.00595

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over