5-170107169-A-G

Position:

• chr5-170107169-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXI1	NM_012188.5	c.574+638A>G		intron_variant		ENST00000306268.8	NP_036320.2
FOXI1	NM_144769.4	c.574+638A>G		intron_variant			NP_658982.1
FOXI1	XR_941092.2	n.780+108A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXI1	ENST00000306268.8	c.574+638A>G		intron_variant		1	NM_012188.5	ENSP00000304286.5
FOXI1	ENST00000449804.4	c.574+638A>G		intron_variant		1		ENSP00000415483.2

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

Gnomad4 AFR exome AF: 0.819

Gnomad4 AMR exome AF: 0.833

Gnomad4 ASJ exome AF: 0.485

Gnomad4 EAS exome AF: 0.820

Gnomad4 SAS exome AF: 0.720

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.575

Gnomad4 OTH exome AF: 0.643

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

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.601

Alfa AF: 0.580 Hom.: 25059

Bravo AF: 0.647

Asia WGS AF: 0.693 AC: 2408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.64

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: rs4315934; hg19: chr5-169534173;