rs4854022

Variant names:

• chr2-240141237-C-G
• rs4854022
• ENST00000391989.6:c.-192-544G>C

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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOS	ENST00000391989.6	c.-192-544G>C		intron_variant	Intron 1 of 4	3		ENSP00000375849.2

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;