rs6555888

Variant names:

• chr5-170109146-A-G
• rs6555888
• NM_012188.5:c.*535A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-170109146-A-G
• chr5-170109146-A-C
• chr5-170109146-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012188.5(FOXI1):​c.*535A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 153,512 control chromosomes in the GnomAD database, including 51,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (51310 hom., cov: 31)
  • Exomes 𝑓: 0.79 (468 hom.)
• Consequence: FOXI1 NM_012188.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-170109146-A-G is Benign according to our data. Variant chr5-170109146-A-G is described in ClinVar as Benign. ClinVar VariationId is 352719.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 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.*535A>G		3_prime_UTR	Exon 2 of 2	NP_036320.2
	FOXI1	NM_144769.4		c.*535A>G		3_prime_UTR	Exon 2 of 2	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.*535A>G		3_prime_UTR	Exon 2 of 2	ENSP00000304286.5	Q12951-1
	FOXI1	ENST00000449804.4	TSL:1	c.*535A>G		3_prime_UTR	Exon 2 of 2	ENSP00000415483.2	Q12951-2

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124646 AN: 151940 Hom.: 51267 Cov.: 31

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.828

GnomAD4 exome AF: 0.794 AC: 1154 AN: 1454 Hom.: 468 Cov.: 0 AF XY: 0.805 AC XY: 605 AN XY: 752

African (AFR) AF: 0.929 AC: 13 AN: 14

American (AMR) AF: 0.839 AC: 208 AN: 248

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 4 AN: 4

East Asian (EAS) AF: 1.00 AC: 14 AN: 14

South Asian (SAS) AF: 0.922 AC: 59 AN: 64

European-Finnish (FIN) AF: 0.737 AC: 28 AN: 38

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.776 AC: 788 AN: 1016

Other (OTH) AF: 0.714 AC: 40 AN: 56

GnomAD4 genome AF: 0.820 AC: 124744 AN: 152058 Hom.: 51310 Cov.: 31 AF XY: 0.820 AC XY: 60928 AN XY: 74308

African (AFR) AF: 0.833 AC: 34535 AN: 41482

American (AMR) AF: 0.854 AC: 13047 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 3013 AN: 3470

East Asian (EAS) AF: 0.941 AC: 4859 AN: 5164

South Asian (SAS) AF: 0.902 AC: 4343 AN: 4814

European-Finnish (FIN) AF: 0.722 AC: 7621 AN: 10560

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.805 AC: 54687 AN: 67968

Other (OTH) AF: 0.830 AC: 1754 AN: 2114

Alfa AF: 0.813 Hom.: 142329

Bravo AF: 0.829

Asia WGS AF: 0.902 AC: 3137 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal recessive nonsyndromic hearing loss 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.23
DANN	Benign	0.64
PhyloP100		-1.1
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

Other links and lift over

dbSNP: rs6555888; hg19: chr5-169536150;