rs113275496

Variant names:

• chr11-17596164-C-A
• rs113275496
• NM_001292063.2:c.3525+10C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-17596164-C-A
• chr11-17596164-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001292063.2(OTOG):​c.3525+10C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000807 in 1,539,728 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (4 hom.)
• Consequence: OTOG NM_001292063.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0480
• 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), PanelApp Australia, 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 11-17596164-C-A is Benign according to our data. Variant chr11-17596164-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00418 (637/152230) while in subpopulation AFR AF = 0.0145 (602/41532). AF 95% confidence interval is 0.0135. There are 5 homozygotes in GnomAd4. There are 284 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.3525+10C>A		intron	N/A	NP_001278992.1
	OTOG	NM_001277269.2		c.3561+10C>A		intron	N/A	NP_001264198.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOG	ENST00000399397.6	TSL:5 MANE Select	c.3525+10C>A		intron	N/A	ENSP00000382329.2
	OTOG	ENST00000399391.7	TSL:5	c.3561+10C>A		intron	N/A	ENSP00000382323.2
	OTOG	ENST00000342528.2	TSL:2	n.890+10C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00418 AC: 636 AN: 152112 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.000979 AC: 146 AN: 149166 AF XY: 0.000760

Gnomad AFR exome AF: 0.0165

Gnomad AMR exome AF: 0.00118

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000545

Gnomad OTH exome AF: 0.000232

GnomAD4 exome AF: 0.000437 AC: 606 AN: 1387498 Hom.: 4 Cov.: 28 AF XY: 0.000349 AC XY: 239 AN XY: 685120

African (AFR) AF: 0.0137 AC: 431 AN: 31372

American (AMR) AF: 0.00151 AC: 54 AN: 35684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25140

East Asian (EAS) AF: 0.00 AC: 0 AN: 35666

South Asian (SAS) AF: 0.0000633 AC: 5 AN: 79006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48174

Middle Eastern (MID) AF: 0.000528 AC: 3 AN: 5678

European-Non Finnish (NFE) AF: 0.0000449 AC: 48 AN: 1069126

Other (OTH) AF: 0.00113 AC: 65 AN: 57652

GnomAD4 genome AF: 0.00418 AC: 637 AN: 152230 Hom.: 5 Cov.: 32 AF XY: 0.00382 AC XY: 284 AN XY: 74440

African (AFR) AF: 0.0145 AC: 602 AN: 41532

American (AMR) AF: 0.00150 AC: 23 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68004

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00307 Hom.: 1

Bravo AF: 0.00470

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		-0.048
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs113275496; hg19: chr11-17617711;