12-80278284-A-G

Variant names:

• chr12-80278284-A-G
• rs1376384
• NM_001378609.3:c.2789+9A>G

Variant summary

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

The NM_001378609.3(OTOGL):​c.2789+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 1,494,294 control chromosomes in the GnomAD database, including 352,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (32393 hom., cov: 32)
  • Exomes 𝑓: 0.69 (320263 hom.)
• Consequence: OTOGL NM_001378609.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.220

Genes affected

OTOGL (HGNC:26901): (otogelin like) The protein encoded by this gene belongs to the otogelin family. This gene is expressed in the inner ear of vertebrates with the highest level of expression seen at the embryonic stage and lowest in adult. Knockdown studies in zebrafish suggest that this gene is essential for normal inner ear function. Mutations in this gene are associated with autosomal recessive deafness. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 12-80278284-A-G is Benign according to our data. Variant chr12-80278284-A-G is described in ClinVar as [Benign]. Clinvar id is 226934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-80278284-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOGL	NM_001378609.3	c.2789+9A>G		intron_variant	Intron 25 of 58	ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOGL	ENST00000547103.7	c.2789+9A>G		intron_variant	Intron 25 of 58	5	NM_001378609.3	ENSP00000447211.2
OTOGL	ENST00000646859.1	c.2789+9A>G		intron_variant	Intron 30 of 62			ENSP00000496036.1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 96810 AN: 151072 Hom.: 32373 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.667

GnomAD3 exomes AF: 0.726 AC: 103385 AN: 142410 Hom.: 38378 AF XY: 0.719 AC XY: 54940 AN XY: 76390

Gnomad AFR exome AF: 0.447

Gnomad AMR exome AF: 0.807

Gnomad ASJ exome AF: 0.674

Gnomad EAS exome AF: 0.934

Gnomad SAS exome AF: 0.697

Gnomad FIN exome AF: 0.818

Gnomad NFE exome AF: 0.675

Gnomad OTH exome AF: 0.693

GnomAD4 exome AF: 0.686 AC: 921933 AN: 1343104 Hom.: 320263 Cov.: 24 AF XY: 0.687 AC XY: 456073 AN XY: 664176

Gnomad4 AFR exome AF: 0.442

Gnomad4 AMR exome AF: 0.797

Gnomad4 ASJ exome AF: 0.672

Gnomad4 EAS exome AF: 0.963

Gnomad4 SAS exome AF: 0.694

Gnomad4 FIN exome AF: 0.810

Gnomad4 NFE exome AF: 0.675

Gnomad4 OTH exome AF: 0.686

GnomAD4 genome AF: 0.641 AC: 96875 AN: 151190 Hom.: 32393 Cov.: 32 AF XY: 0.651 AC XY: 48071 AN XY: 73894

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.680

Gnomad4 EAS AF: 0.937

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.670

Alfa AF: 0.669 Hom.: 47466

Bravo AF: 0.626

Asia WGS AF: 0.807 AC: 2806 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

c.2762+9A>G in intron 24 of OTOGL: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence. It has been identified in 98.3% (175/178) of Japanese chromosomes from a broad population by the 1000 Genomes Project (http://www.ncbi.nlm.nih.gov/proje cts/SNP; dbSNP rs1376384). -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 09, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.0
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1376384; hg19: chr12-80672064;