rs538124093

Variant names:

• chr11-17634960-G-A
• rs538124093
• NM_001292063.2:c.7585+12G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-17634960-G-A
• chr11-17634960-G-C

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.7585+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000651 in 1,517,650 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (4 hom.)
• Consequence: OTOG NM_001292063.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.09
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-17634960-G-A is Benign according to our data. Variant chr11-17634960-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 227794.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 = 0.00315 (478/151846) while in subpopulation AFR AF = 0.0109 (451/41420). AF 95% confidence interval is 0.0101. There are 2 homozygotes in GnomAd4. There are 231 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 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.7585+12G>A		intron	N/A	NP_001278992.1	H9KVB3
	OTOG	NM_001277269.2		c.7621+12G>A		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+12G>A		intron	N/A	ENSP00000382329.2	H9KVB3
	OTOG	ENST00000399391.7	TSL:5	c.7621+12G>A		intron	N/A	ENSP00000382323.2	Q6ZRI0-1
	OTOG	ENST00000342528.2	TSL:2	n.4606-650G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00307 AC: 466 AN: 151728 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00434

GnomAD2 exomes AF: 0.000720 AC: 102 AN: 141610 AF XY: 0.000546

Gnomad AFR exome AF: 0.0120

Gnomad AMR exome AF: 0.000835

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000117

Gnomad OTH exome AF: 0.000243

GnomAD4 exome AF: 0.000373 AC: 510 AN: 1365804 Hom.: 4 Cov.: 31 AF XY: 0.000332 AC XY: 224 AN XY: 674910

African (AFR) AF: 0.0105 AC: 321 AN: 30554

American (AMR) AF: 0.000845 AC: 30 AN: 35520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24840

East Asian (EAS) AF: 0.00 AC: 0 AN: 35592

South Asian (SAS) AF: 0.0000255 AC: 2 AN: 78356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47618

Middle Eastern (MID) AF: 0.000399 AC: 2 AN: 5010

European-Non Finnish (NFE) AF: 0.0000932 AC: 98 AN: 1051450

Other (OTH) AF: 0.00100 AC: 57 AN: 56864

GnomAD4 genome AF: 0.00315 AC: 478 AN: 151846 Hom.: 2 Cov.: 32 AF XY: 0.00311 AC XY: 231 AN XY: 74234

African (AFR) AF: 0.0109 AC: 451 AN: 41420

American (AMR) AF: 0.000720 AC: 11 AN: 15272

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67846

Other (OTH) AF: 0.00429 AC: 9 AN: 2098

Alfa AF: 0.000218 Hom.: 0

Bravo AF: 0.00345

Asia WGS AF: 0.00115 AC: 4 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign/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	-0.90
CADD	Benign	0.0010
DANN	Benign	0.46
PhyloP100		-3.1
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: rs538124093; hg19: chr11-17656507;