chr8-132039304-C-T

Variant names:

• chr8-132039304-C-T
• rs2102103
• NM_001080399.3:c.458-181G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ENSG00000258417 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OC90	NM_001080399.3	c.458-181G>A		intron_variant	Intron 6 of 13	ENST00000254627.4	NP_001073868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OC90	ENST00000254627.4	c.458-181G>A		intron_variant	Intron 6 of 13	2	NM_001080399.3	ENSP00000254627.3
ENSG00000258417	ENST00000262283.5	c.1046-181G>A		intron_variant	Intron 9 of 17	5		ENSP00000262283.5

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

African (AFR) AF: 0.220 AC: 9088 AN: 41380

American (AMR) AF: 0.462 AC: 7051 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1351 AN: 3472

East Asian (EAS) AF: 0.507 AC: 2606 AN: 5140

South Asian (SAS) AF: 0.372 AC: 1792 AN: 4812

European-Finnish (FIN) AF: 0.359 AC: 3785 AN: 10550

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.382 AC: 25971 AN: 67918

Other (OTH) AF: 0.374 AC: 790 AN: 2110

Alfa AF: 0.371 Hom.: 43917

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
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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