rs2879269

Variant names:

• chr5-170107529-G-A
• rs2879269
• NM_012188.5:c.575-520G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-170107529-G-A
• chr5-170107529-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012188.5(FOXI1):​c.575-520G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.915 in 152,204 control chromosomes in the GnomAD database, including 63,792 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 0.92 (63792 hom., cov: 31)
• Consequence: FOXI1 NM_012188.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.451

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXI1	NM_012188.5	c.575-520G>A		intron_variant	Intron 1 of 1	ENST00000306268.8	NP_036320.2
FOXI1	NM_144769.4	c.575-805G>A		intron_variant	Intron 1 of 1		NP_658982.1
FOXI1	XR_941092.2	n.780+468G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXI1	ENST00000306268.8	c.575-520G>A		intron_variant	Intron 1 of 1	1	NM_012188.5	ENSP00000304286.5
FOXI1	ENST00000449804.4	c.575-805G>A		intron_variant	Intron 1 of 1	1		ENSP00000415483.2

Frequencies

GnomAD3 genomes AF: 0.915 AC: 139160 AN: 152086 Hom.: 63741 Cov.: 31

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.909

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.915 AC: 139268 AN: 152204 Hom.: 63792 Cov.: 31 AF XY: 0.913 AC XY: 67944 AN XY: 74406

Gnomad4 AFR AF: 0.927

Gnomad4 AMR AF: 0.917

Gnomad4 ASJ AF: 0.952

Gnomad4 EAS AF: 0.986

Gnomad4 SAS AF: 0.933

Gnomad4 FIN AF: 0.864

Gnomad4 NFE AF: 0.908

Gnomad4 OTH AF: 0.910

Alfa AF: 0.912 Hom.: 27161

Bravo AF: 0.919

Asia WGS AF: 0.947 AC: 3294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.043
DANN	Benign	0.55

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: rs2879269; hg19: chr5-169534533;