rs182750732

Variant names:

• chr11-17645736-C-T
• rs182750732
• NM_001292063.2:c.8542-8C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-17645736-C-T
• chr11-17645736-C-A

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.8542-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00865 in 1,550,846 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0055 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0090 (78 hom.)
• Consequence: OTOG NM_001292063.2 splice_region, intron
• Scores: Splicing: ADA: 0.00004959
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.61
• 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]

LINC02729 (HGNC:54246): (long intergenic non-protein coding RNA 2729)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 11-17645736-C-T is Benign according to our data. Variant chr11-17645736-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226922.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0055 (838/152362) while in subpopulation NFE AF = 0.00967 (658/68032). AF 95% confidence interval is 0.00906. There are 5 homozygotes in GnomAd4. There are 368 alleles in the male GnomAd4 subpopulation. Median coverage is 33. 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.8542-8C>T		splice_region intron	N/A	NP_001278992.1	H9KVB3
	OTOG	NM_001277269.2		c.8578-8C>T		splice_region 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.8542-8C>T		splice_region intron	N/A	ENSP00000382329.2	H9KVB3
	OTOG	ENST00000399391.7	TSL:5	c.8578-8C>T		splice_region intron	N/A	ENSP00000382323.2	Q6ZRI0-1
	LINC02729	ENST00000849122.1		n.196-663G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00550 AC: 838 AN: 152244 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00967

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00463 AC: 695 AN: 150154 AF XY: 0.00487

Gnomad AFR exome AF: 0.00145

Gnomad AMR exome AF: 0.00264

Gnomad ASJ exome AF: 0.00179

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000651

Gnomad NFE exome AF: 0.0101

Gnomad OTH exome AF: 0.00460

GnomAD4 exome AF: 0.00899 AC: 12571 AN: 1398484 Hom.: 78 Cov.: 32 AF XY: 0.00868 AC XY: 5988 AN XY: 689750

African (AFR) AF: 0.00136 AC: 43 AN: 31598

American (AMR) AF: 0.00246 AC: 88 AN: 35706

Ashkenazi Jewish (ASJ) AF: 0.00187 AC: 47 AN: 25182

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35740

South Asian (SAS) AF: 0.000745 AC: 59 AN: 79234

European-Finnish (FIN) AF: 0.00112 AC: 54 AN: 48282

Middle Eastern (MID) AF: 0.00175 AC: 10 AN: 5700

European-Non Finnish (NFE) AF: 0.0110 AC: 11885 AN: 1079000

Other (OTH) AF: 0.00662 AC: 384 AN: 58042

GnomAD4 genome AF: 0.00550 AC: 838 AN: 152362 Hom.: 5 Cov.: 33 AF XY: 0.00494 AC XY: 368 AN XY: 74508

African (AFR) AF: 0.00144 AC: 60 AN: 41584

American (AMR) AF: 0.00490 AC: 75 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4826

European-Finnish (FIN) AF: 0.000847 AC: 9 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00967 AC: 658 AN: 68032

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00759 Hom.: 3

Bravo AF: 0.00550

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	not specified (2)
-	-	1	OTOG-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.1
DANN	Benign	0.62
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000050
dbscSNV1_RF	Benign	0.022
SpliceAI score (max)		0.020		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: rs182750732; hg19: chr11-17667283;