rs4854022

chr2-240141237-C-G

Variant summary

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

The ENST00000391989.6(OTOS):c.-192-544G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,162 control chromosomes in the GnomAD database, including 4,454 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 0.24 (4454 hom., cov: 33)
• Consequence: OTOS ENST00000391989.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

Genes affected

OTOS (HGNC:22644): (otospiralin) Otospiralin is synthesized by nonsensory cells (fibrocytes) of the inner ear, and downregulation of otospiralin in guinea pigs leads to deafness (Lavigne-Rebillard et al., 2003 [PubMed 12687421]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 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
OTOS	ENST00000391989.6	c.-192-544G>C		intron_variant		3		P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36488 AN: 152044 Hom.: 4447 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.240 AC: 36504 AN: 152162 Hom.: 4454 Cov.: 33 AF XY: 0.239 AC XY: 17781 AN XY: 74390

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.244

Alfa AF: 0.235 Hom.: 625

Bravo AF: 0.242

Asia WGS AF: 0.182 AC: 636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.49
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs4854022; hg19: chr2-241080654;