12-80210987-A-G

Position:

• chr12-80210987-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001378609.3(OTOGL):​c.119+101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0205 in 736,440 control chromosomes in the GnomAD database, including 218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (21 hom., cov: 32)
  • Exomes 𝑓: 0.022 (197 hom.)
• Consequence: OTOGL NM_001378609.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.500

Genes affected

OTOGL (HGNC:26901): (otogelin like) The protein encoded by this gene belongs to the otogelin family. This gene is expressed in the inner ear of vertebrates with the highest level of expression seen at the embryonic stage and lowest in adult. Knockdown studies in zebrafish suggest that this gene is essential for normal inner ear function. Mutations in this gene are associated with autosomal recessive deafness. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 12-80210987-A-G is Benign according to our data. Variant chr12-80210987-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1211128.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 = 0.0138 (2101/152220) while in subpopulation NFE AF= 0.0235 (1601/67988). AF 95% confidence interval is 0.0226. There are 21 homozygotes in gnomad4. There are 983 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOGL	NM_001378609.3	c.119+101A>G		intron_variant		ENST00000547103.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOGL	ENST00000547103.7	c.119+101A>G		intron_variant		5	NM_001378609.3	P1
OTOGL	ENST00000646859.1	c.119+101A>G		intron_variant
OTOGL	ENST00000643417.1	n.779+101A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2101 AN: 152102 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.00427

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00544

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00829

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0235

Gnomad OTH AF: 0.00958

GnomAD4 exome AF: 0.0222 AC: 12969 AN: 584220 Hom.: 197 AF XY: 0.0216 AC XY: 6317 AN XY: 291992

Gnomad4 AFR exome AF: 0.00421

Gnomad4 AMR exome AF: 0.00563

Gnomad4 ASJ exome AF: 0.0131

Gnomad4 EAS exome AF: 0.000123

Gnomad4 SAS exome AF: 0.00890

Gnomad4 FIN exome AF: 0.00874

Gnomad4 NFE exome AF: 0.0260

Gnomad4 OTH exome AF: 0.0222

GnomAD4 genome AF: 0.0138 AC: 2101 AN: 152220 Hom.: 21 Cov.: 32 AF XY: 0.0132 AC XY: 983 AN XY: 74422

Gnomad4 AFR AF: 0.00426

Gnomad4 AMR AF: 0.00543

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00829

Gnomad4 FIN AF: 0.0107

Gnomad4 NFE AF: 0.0235

Gnomad4 OTH AF: 0.00948

Alfa AF: 0.0194 Hom.: 9

Bravo AF: 0.0126

Asia WGS AF: 0.00290 AC: 10 AN: 3466

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 22, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.9
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs80086846; hg19: chr12-80604767;