rs72828668

Variant names:

• chr5-170108942-G-C
• rs72828668
• NM_012188.5:c.*331G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-170108942-G-C
• chr5-170108942-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012188.5(FOXI1):​c.*331G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 294,548 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (51 hom., cov: 33)
  • Exomes 𝑓: 0.024 (59 hom.)
• Consequence: FOXI1 NM_012188.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.390
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-170108942-G-C is Benign according to our data. Variant chr5-170108942-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 904692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0549 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.*331G>C		3_prime_UTR	Exon 2 of 2	NP_036320.2
	FOXI1	NM_144769.4		c.*331G>C		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.*331G>C		3_prime_UTR	Exon 2 of 2	ENSP00000304286.5	Q12951-1
	FOXI1	ENST00000449804.4	TSL:1	c.*331G>C		3_prime_UTR	Exon 2 of 2	ENSP00000415483.2	Q12951-2

Frequencies

GnomAD3 genomes AF: 0.0205 AC: 3115 AN: 152136 Hom.: 50 Cov.: 33

Gnomad AFR AF: 0.00427

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.0378

Gnomad SAS AF: 0.0602

Gnomad FIN AF: 0.0503

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0226

Gnomad OTH AF: 0.0192

GnomAD4 exome AF: 0.0238 AC: 3387 AN: 142294 Hom.: 59 Cov.: 0 AF XY: 0.0250 AC XY: 1838 AN XY: 73630

African (AFR) AF: 0.00556 AC: 28 AN: 5036

American (AMR) AF: 0.00838 AC: 52 AN: 6208

Ashkenazi Jewish (ASJ) AF: 0.0246 AC: 118 AN: 4800

East Asian (EAS) AF: 0.0305 AC: 286 AN: 9382

South Asian (SAS) AF: 0.0540 AC: 553 AN: 10244

European-Finnish (FIN) AF: 0.0415 AC: 336 AN: 8098

Middle Eastern (MID) AF: 0.0281 AC: 20 AN: 712

European-Non Finnish (NFE) AF: 0.0205 AC: 1826 AN: 89002

Other (OTH) AF: 0.0191 AC: 168 AN: 8812

GnomAD4 genome AF: 0.0205 AC: 3115 AN: 152254 Hom.: 51 Cov.: 33 AF XY: 0.0224 AC XY: 1665 AN XY: 74424

African (AFR) AF: 0.00426 AC: 177 AN: 41556

American (AMR) AF: 0.0150 AC: 229 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 89 AN: 3472

East Asian (EAS) AF: 0.0378 AC: 196 AN: 5180

South Asian (SAS) AF: 0.0607 AC: 292 AN: 4814

European-Finnish (FIN) AF: 0.0503 AC: 533 AN: 10588

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0226 AC: 1536 AN: 68018

Other (OTH) AF: 0.0190 AC: 40 AN: 2110

Alfa AF: 0.0195 Hom.: 6

Bravo AF: 0.0156

Asia WGS AF: 0.0310 AC: 110 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal recessive nonsyndromic hearing loss 4 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.5
DANN	Benign	0.78
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism

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: rs72828668;

hg19: chr5-169535946;