8-132041071-T-C

Variant names:

• chr8-132041071-T-C
• rs7386783
• NM_001080399.3:c.430A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080399.3(OC90):​c.430A>G​(p.Asn144Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 1,603,954 control chromosomes in the GnomAD database, including 416,581 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.73 (40572 hom., cov: 32)
  • Exomes 𝑓: 0.72 (376009 hom.)
• Consequence: OC90 NM_001080399.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 21 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 (MetaRNN=1.195024E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080399.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OC90	NM_001080399.3	MANE Select	c.430A>G	p.Asn144Asp	missense	Exon 6 of 14	NP_001073868.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OC90	ENST00000254627.4	TSL:2 MANE Select	c.430A>G	p.Asn144Asp	missense	Exon 6 of 14	ENSP00000254627.3
	ENSG00000258417	ENST00000262283.5	TSL:5	c.1018A>G	p.Asn340Asp	missense	Exon 9 of 18	ENSP00000262283.5

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110512 AN: 151456 Hom.: 40531 Cov.: 32

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.835

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.676

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.713

GnomAD2 exomes AF: 0.731 AC: 181816 AN: 248786 AF XY: 0.728

Gnomad AFR exome AF: 0.744

Gnomad AMR exome AF: 0.774

Gnomad ASJ exome AF: 0.688

Gnomad EAS exome AF: 0.764

Gnomad FIN exome AF: 0.729

Gnomad NFE exome AF: 0.716

Gnomad OTH exome AF: 0.728

GnomAD4 exome AF: 0.719 AC: 1043700 AN: 1452384 Hom.: 376009 Cov.: 34 AF XY: 0.718 AC XY: 519075 AN XY: 722996

African (AFR) AF: 0.744 AC: 24790 AN: 33320

American (AMR) AF: 0.772 AC: 34505 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 17894 AN: 26086

East Asian (EAS) AF: 0.762 AC: 30228 AN: 39652

South Asian (SAS) AF: 0.727 AC: 62580 AN: 86074

European-Finnish (FIN) AF: 0.734 AC: 39149 AN: 53368

Middle Eastern (MID) AF: 0.682 AC: 3919 AN: 5748

European-Non Finnish (NFE) AF: 0.714 AC: 787692 AN: 1103382

Other (OTH) AF: 0.715 AC: 42943 AN: 60048

GnomAD4 genome AF: 0.730 AC: 110609 AN: 151570 Hom.: 40572 Cov.: 32 AF XY: 0.729 AC XY: 53987 AN XY: 74026

African (AFR) AF: 0.743 AC: 30690 AN: 41318

American (AMR) AF: 0.751 AC: 11467 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2318 AN: 3466

East Asian (EAS) AF: 0.761 AC: 3868 AN: 5084

South Asian (SAS) AF: 0.723 AC: 3476 AN: 4810

European-Finnish (FIN) AF: 0.725 AC: 7616 AN: 10504

Middle Eastern (MID) AF: 0.679 AC: 197 AN: 290

European-Non Finnish (NFE) AF: 0.718 AC: 48727 AN: 67824

Other (OTH) AF: 0.709 AC: 1495 AN: 2108

Alfa AF: 0.717 Hom.: 175063

Bravo AF: 0.734

TwinsUK AF: 0.709 AC: 2629

ALSPAC AF: 0.714 AC: 2753

ESP6500AA AF: 0.751 AC: 3035

ESP6500EA AF: 0.717 AC: 5988

ExAC AF: 0.729 AC: 88064

Asia WGS AF: 0.732 AC: 2547 AN: 3478

EpiCase AF: 0.704

EpiControl AF: 0.705

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.17
DEOGEN2	Benign	0.037	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.095	N
PhyloP100		0.25
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.031
Sift	Benign	1.0	T
Sift4G	Benign	0.79	T
Polyphen		0.0	B
Vest4		0.070
MPC		0.0028
ClinPred		0.000013	T
GERP RS		1.1
Varity_R		0.039
gMVP		0.36
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: rs7386783; hg19: chr8-133053318; COSMIC: COSV51839865;