rs4491792

Positions:

• chr20-16760180-T-C
• chr20-16760180-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000490148.1(OTOR):​n.102-4142T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 151,334 control chromosomes in the GnomAD database, including 3,382 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3382 hom., cov: 31)
• Consequence: OTOR ENST00000490148.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313

Genes affected

OTOR (HGNC:8517): (otoraplin) This gene encodes a member of the melanoma-inhibiting activity gene family. The encoded protein is secreted via the Golgi apparatus and may function in cartilage development and maintenance. A frequent polymorphism in the translation start codon of this gene can abolish translation and may be associated with forms of deafness. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOR	ENST00000490148.1	n.102-4142T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31318 AN: 151212 Hom.: 3376 Cov.: 31

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.0794

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.202

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.207 AC: 31353 AN: 151334 Hom.: 3382 Cov.: 31 AF XY: 0.204 AC XY: 15086 AN XY: 73910

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.0792

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.204

Alfa AF: 0.181 Hom.: 2651

Bravo AF: 0.219

Asia WGS AF: 0.161 AC: 559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4491792; hg19: chr20-16740825;