rs778915475

Variant names:

• chr11-17641903-C-T
• rs778915475
• NM_001292063.2:c.8247C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-17641903-C-T
• chr11-17641903-C-A
• chr11-17641903-C-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001292063.2(OTOG):​c.8247C>T​(p.Asn2749Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,550,330 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 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: OTOG NM_001292063.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.44
• 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-17641903-C-T is Benign according to our data. Variant chr11-17641903-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 227807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.44 with no splicing effect.

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.8247C>T	p.Asn2749Asn	synonymous	Exon 52 of 56	NP_001278992.1	H9KVB3
	OTOG	NM_001277269.2		c.8283C>T	p.Asn2761Asn	synonymous	Exon 51 of 55	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.8247C>T	p.Asn2749Asn	synonymous	Exon 52 of 56	ENSP00000382329.2	H9KVB3
	OTOG	ENST00000399391.7	TSL:5	c.8283C>T	p.Asn2761Asn	synonymous	Exon 51 of 55	ENSP00000382323.2	Q6ZRI0-1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

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: 0.0000606 AC: 9 AN: 148634 AF XY: 0.0000624

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000408

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000742

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000129 AC: 18 AN: 1398118 Hom.: 0 Cov.: 33 AF XY: 0.0000116 AC XY: 8 AN XY: 689600

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.0000280 AC: 1 AN: 35686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25174

East Asian (EAS) AF: 0.000280 AC: 10 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000556 AC: 6 AN: 1078858

Other (OTH) AF: 0.0000172 AC: 1 AN: 57992

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74440

African (AFR) AF: 0.00 AC: 0 AN: 41530

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

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	-0.79
CADD	Benign	0.057
DANN	Benign	0.50
PhyloP100		-2.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs778915475; hg19: chr11-17663450; COSMIC: COSV107428884; COSMIC: COSV107428884;