Variant chr16-21678470-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_144672.4(OTOA):c.-4-41T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,180,340 control chromosomes in the GnomAD database, including 72,595 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8726 hom., cov: 30)

Exomes 𝑓: 0.37 ( 63869 hom. )

Consequence

OTOA
NM_144672.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.340

Variant links:

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]

OTOA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 16-21678470-T-A is Benign according to our data. Variant chr16-21678470-T-A is described in ClinVar as [Benign]. Clinvar id is 1287638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOA	NM_144672.4 linkuse as main transcript	c.-4-41T>A		intron_variant		ENST00000646100.2	NP_653273.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
OTOA	ENST00000646100.2 linkuse as main transcript	c.-4-41T>A	intron_variant		NM_144672.4	ENSP00000496564	P2	Q7RTW8-5
OTOA	ENST00000647277.1 linkuse as main transcript	c.-4-41T>A	intron_variant, NMD_transcript_variant			ENSP00000495594
OTOA	ENST00000388958.8 linkuse as main transcript		upstream_gene_variant	1		ENSP00000373610	P2	Q7RTW8-5
OTOA	ENST00000286149.8 linkuse as main transcript		upstream_gene_variant	5		ENSP00000286149	A2	Q7RTW8-1

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

46981

AN:

149274

Hom.:

8723

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.369

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.416

Gnomad FIN

AF:

0.376

Gnomad MID

AF:

0.319

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.335

GnomAD3 exomes

AF:

0.314

AC:

65489

AN:

208754

Hom.:

7691

AF XY:

0.321

AC XY:

36243

AN XY:

112858

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.287

Gnomad ASJ exome

AF:

0.329

Gnomad EAS exome

AF:

0.110

Gnomad SAS exome

AF:

0.363

Gnomad FIN exome

AF:

0.339

Gnomad NFE exome

AF:

0.367

Gnomad OTH exome

AF:

0.344

GnomAD4 exome

AF:

0.369

AC:

380202

AN:

1030970

Hom.:

63869

Cov.:

AF XY:

0.371

AC XY:

196006

AN XY:

528140

show subpopulations

Gnomad4 AFR exome

AF:

0.0995

Gnomad4 AMR exome

AF:

0.297

Gnomad4 ASJ exome

AF:

0.340

Gnomad4 EAS exome

AF:

0.100

Gnomad4 SAS exome

AF:

0.387

Gnomad4 FIN exome

AF:

0.344

Gnomad4 NFE exome

AF:

0.396

Gnomad4 OTH exome

AF:

0.344

GnomAD4 genome

AF:

0.315

AC:

46983

AN:

149370

Hom.:

8726

Cov.:

AF XY:

0.311

AC XY:

22703

AN XY:

72920

show subpopulations

Gnomad4 AFR

AF:

0.114

Gnomad4 AMR

AF:

0.315

Gnomad4 ASJ

AF:

0.369

Gnomad4 EAS

AF:

0.116

Gnomad4 SAS

AF:

0.417

Gnomad4 FIN

AF:

0.376

Gnomad4 NFE

AF:

0.426

Gnomad4 OTH

AF:

0.338

Alfa

AF:

0.360

Hom.:

1782

Bravo

AF:

0.301

Asia WGS

AF:

0.261

AC:

908

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Jun 24, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.7

DANN

Benign

0.24

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over