chr2-240141237-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000391989.6. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOS	ENST00000391989.6	TSL:3	c.-192-544G>C		intron	N/A	ENSP00000375849.2	Q8NHW6

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

African (AFR) AF: 0.281 AC: 11663 AN: 41490

American (AMR) AF: 0.234 AC: 3588 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 702 AN: 3472

East Asian (EAS) AF: 0.153 AC: 792 AN: 5168

South Asian (SAS) AF: 0.203 AC: 981 AN: 4822

European-Finnish (FIN) AF: 0.236 AC: 2506 AN: 10604

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15595 AN: 67986

Other (OTH) AF: 0.244 AC: 515 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.49
DANN	Benign	0.69
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4854022; hg19: chr2-241080654;