8-132039304-C-T

Position:

• chr8-132039304-C-T

Variant summary

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

The NM_001080399.3(OC90):​c.458-181G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,856 control chromosomes in the GnomAD database, including 9,948 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 0.35 (9948 hom., cov: 31)
• Consequence: OC90 NM_001080399.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.906

Genes affected

OC90 (HGNC:8100): (otoconin 90) Predicted to enable calcium ion binding activity and structural molecule activity. Predicted to be involved in otolith mineralization. Predicted to be located in extracellular region. Predicted to be active in extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OC90	NM_001080399.3	c.458-181G>A		intron_variant		ENST00000254627.4	NP_001073868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OC90	ENST00000254627.4	c.458-181G>A		intron_variant		2	NM_001080399.3	ENSP00000254627	P1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53037 AN: 151736 Hom.: 9934 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.394

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.350 AC: 53082 AN: 151856 Hom.: 9948 Cov.: 31 AF XY: 0.354 AC XY: 26245 AN XY: 74190

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.374

Alfa AF: 0.373 Hom.: 20995

Bravo AF: 0.354

Asia WGS AF: 0.431 AC: 1497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.70

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: rs2102103; hg19: chr8-133051551; COSMIC: COSV51841140;