16-21728953-C-T

Variant names:

• chr16-21728953-C-T
• rs8050407
• NM_144672.4:c.2207+522C>T

Variant summary

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

The NM_144672.4(OTOA):​c.2207+522C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,024 control chromosomes in the GnomAD database, including 4,715 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 0.24 (4715 hom., cov: 31)
• Consequence: OTOA NM_144672.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.584

Genes affected

OTOA (HGNC:16378): (otoancorin) The protein encoded by this gene is specifically expressed in the inner ear, and is located at the interface between the apical surface of the inner ear sensory epithelia and their overlying acellular gels. It is prposed that this protein is involved in the attachment of the inner ear acellular gels to the apical surface of the underlying nonsensory cells. Mutations in this gene are associated with autosomal recessive deafness type 22 (DFNB22). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOA	NM_144672.4	c.2207+522C>T		intron_variant	Intron 20 of 28	ENST00000646100.2	NP_653273.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOA	ENST00000646100.2	c.2207+522C>T		intron_variant	Intron 20 of 28		NM_144672.4	ENSP00000496564.2

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36969 AN: 151906 Hom.: 4714 Cov.: 31

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.243 AC: 36975 AN: 152024 Hom.: 4715 Cov.: 31 AF XY: 0.238 AC XY: 17714 AN XY: 74302

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.256

Alfa AF: 0.254 Hom.: 3072

Bravo AF: 0.239

Asia WGS AF: 0.140 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.9
DANN	Benign	0.73

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: rs8050407; hg19: chr16-21740274;