chr16-21678454-G-A

Position:

• chr16-21678454-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144672.4(OTOA):​c.-4-57G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 861,546 control chromosomes in the GnomAD database, including 1,790 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (451 hom., cov: 31)
  • Exomes 𝑓: 0.025 (1339 hom.)
• Consequence: OTOA NM_144672.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.793

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-21678454-G-A is Benign according to our data. Variant chr16-21678454-G-A is described in ClinVar as [Benign]. Clinvar id is 1259589.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOA	NM_144672.4	c.-4-57G>A		intron_variant		ENST00000646100.2	NP_653273.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTOA	ENST00000646100.2	c.-4-57G>A		intron_variant			NM_144672.4	ENSP00000496564.2
OTOA	ENST00000647277.1	n.-4-57G>A		intron_variant				ENSP00000495594.1

Frequencies

GnomAD3 genomes AF: 0.0500 AC: 7466 AN: 149466 Hom.: 448 Cov.: 31

Gnomad AFR AF: 0.0798

Gnomad AMI AF: 0.00771

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0325

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.0501

Gnomad FIN AF: 0.00954

Gnomad MID AF: 0.0194

Gnomad NFE AF: 0.00944

Gnomad OTH AF: 0.0564

GnomAD4 exome AF: 0.0249 AC: 17723 AN: 712018 Hom.: 1339 AF XY: 0.0248 AC XY: 9239 AN XY: 372786

Gnomad4 AFR exome AF: 0.0482

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.0225

Gnomad4 EAS exome AF: 0.260

Gnomad4 SAS exome AF: 0.0270

Gnomad4 FIN exome AF: 0.00970

Gnomad4 NFE exome AF: 0.00606

Gnomad4 OTH exome AF: 0.0265

GnomAD4 genome AF: 0.0500 AC: 7475 AN: 149528 Hom.: 451 Cov.: 31 AF XY: 0.0519 AC XY: 3785 AN XY: 72888

Gnomad4 AFR AF: 0.0799

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0325

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.0496

Gnomad4 FIN AF: 0.00954

Gnomad4 NFE AF: 0.00942

Gnomad4 OTH AF: 0.0549

Alfa AF: 0.0329 Hom.: 37

Bravo AF: 0.0658

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 15, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs77996753; hg19: chr16-21689775; COSMIC: COSV53752342; COSMIC: COSV53752342;