11-17634959-C-T

Variant names:

• chr11-17634959-C-T
• rs369343034
• NM_001292063.2:c.7585+11C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_001292063.2(OTOG):​c.7585+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000267 in 483,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00010 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00031 (0 hom.)
• Consequence: OTOG NM_001292063.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.18
• Publications: 0 publications found

Genes affected

OTOG (HGNC:8516): (otogelin) The protein encoded by this gene is a component of the acellular membranes of the inner ear. Disruption of the orthologous mouse gene shows that it plays a role in auditory and vestibular functions. It is involved in fibrillar network organization, the anchoring of otoconial membranes and cupulae to the neuroepithelia, and likely in sound stimulation resistance. Mutations in this gene cause autosomal recessive nonsyndromic deafness, type 18B. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]

OTOG Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 18B

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 11-17634959-C-T is Benign according to our data. Variant chr11-17634959-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 506129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.000308 (119/386112) while in subpopulation EAS AF = 0.00684 (72/10528). AF 95% confidence interval is 0.00557. There are 0 homozygotes in GnomAdExome4. There are 60 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001292063.2. 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
	OTOG	NM_001292063.2	MANE Select	c.7585+11C>T		intron	N/A	NP_001278992.1	H9KVB3
	OTOG	NM_001277269.2		c.7621+11C>T		intron	N/A	NP_001264198.1	Q6ZRI0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOG	ENST00000399397.6	TSL:5 MANE Select	c.7585+11C>T		intron	N/A	ENSP00000382329.2	H9KVB3
	OTOG	ENST00000399391.7	TSL:5	c.7621+11C>T		intron	N/A	ENSP00000382323.2	Q6ZRI0-1
	OTOG	ENST00000342528.2	TSL:2	n.4606-651C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000103 AC: 10 AN: 97184 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00190

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000109 AC: 13 AN: 119620 AF XY: 0.000152

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00123

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000220

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000308 AC: 119 AN: 386112 Hom.: 0 Cov.: 0 AF XY: 0.000289 AC XY: 60 AN XY: 207786

African (AFR) AF: 0.000173 AC: 2 AN: 11534

American (AMR) AF: 0.00 AC: 0 AN: 19772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10108

East Asian (EAS) AF: 0.00684 AC: 72 AN: 10528

South Asian (SAS) AF: 0.0000189 AC: 1 AN: 52944

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2182

European-Non Finnish (NFE) AF: 0.0000252 AC: 6 AN: 237854

Other (OTH) AF: 0.00228 AC: 38 AN: 16636

GnomAD4 genome AF: 0.000103 AC: 10 AN: 97212 Hom.: 0 Cov.: 28 AF XY: 0.000126 AC XY: 6 AN XY: 47444

African (AFR) AF: 0.000150 AC: 4 AN: 26634

American (AMR) AF: 0.00 AC: 0 AN: 9902

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2512

East Asian (EAS) AF: 0.00190 AC: 6 AN: 3154

South Asian (SAS) AF: 0.00 AC: 0 AN: 2742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4774

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 188

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 45408

Other (OTH) AF: 0.00 AC: 0 AN: 1336

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000793

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.56
DANN	Benign	0.55
PhyloP100		-1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs369343034; hg19: chr11-17656506;