rs4315934

Variant names:

• chr5-170107169-A-G
• rs4315934
• NM_012188.5:c.574+638A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-170107169-A-G
• chr5-170107169-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012188.5(FOXI1):​c.574+638A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 165,358 control chromosomes in the GnomAD database, including 34,306 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.64 (31983 hom., cov: 33)
  • Exomes 𝑓: 0.58 (2323 hom.)
• Consequence: FOXI1 NM_012188.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive distal renal tubular acidosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Pendred syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss disorder

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 4

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• enlarged vestibular aqueduct syndrome

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012188.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXI1	NM_012188.5	MANE Select	c.574+638A>G		intron	N/A	NP_036320.2
	FOXI1	NM_144769.4		c.574+638A>G		intron	N/A	NP_658982.1	Q12951-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXI1	ENST00000306268.8	TSL:1 MANE Select	c.574+638A>G		intron	N/A	ENSP00000304286.5	Q12951-1
	FOXI1	ENST00000449804.4	TSL:1	c.574+638A>G		intron	N/A	ENSP00000415483.2	Q12951-2

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97390 AN: 152020 Hom.: 31958 Cov.: 33

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.599

GnomAD4 exome AF: 0.584 AC: 7720 AN: 13218 Hom.: 2323 AF XY: 0.581 AC XY: 3746 AN XY: 6452

African (AFR) AF: 0.819 AC: 167 AN: 204

American (AMR) AF: 0.833 AC: 5 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 32 AN: 66

East Asian (EAS) AF: 0.820 AC: 41 AN: 50

South Asian (SAS) AF: 0.720 AC: 177 AN: 246

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 0.625 AC: 20 AN: 32

European-Non Finnish (NFE) AF: 0.575 AC: 7025 AN: 12220

Other (OTH) AF: 0.643 AC: 252 AN: 392

GnomAD4 genome AF: 0.641 AC: 97458 AN: 152140 Hom.: 31983 Cov.: 33 AF XY: 0.641 AC XY: 47698 AN XY: 74396

African (AFR) AF: 0.770 AC: 31970 AN: 41500

American (AMR) AF: 0.594 AC: 9088 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2017 AN: 3466

East Asian (EAS) AF: 0.821 AC: 4248 AN: 5172

South Asian (SAS) AF: 0.649 AC: 3128 AN: 4820

European-Finnish (FIN) AF: 0.549 AC: 5811 AN: 10588

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39172 AN: 67978

Other (OTH) AF: 0.601 AC: 1270 AN: 2112

Alfa AF: 0.588 Hom.: 34053

Bravo AF: 0.647

Asia WGS AF: 0.693 AC: 2408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.64
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4315934;

hg19: chr5-169534173;