Genetic Variant OR10X1:p.Ile142Ile (chr1-158579474-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001004477.1(OR10X1):c.426C>T(p.Ile142Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,613,512 control chromosomes in the GnomAD database, including 180,715 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 0.50 ( 18944 hom., cov: 30)

Exomes 𝑓: 0.47 ( 161771 hom. )

Consequence

OR10X1
NM_001004477.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.251

Variant links:

Genes affected

OR10X1 (HGNC:14995): (olfactory receptor family 10 subfamily X member 1) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

OR10X1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP7

Synonymous conserved (PhyloP=0.251 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR10X1	NM_001004477.1 link	c.426C>T	p.Ile142Ile	synonymous_variant	Exon 1 of 1	ENST00000623167.1	NP_001004477.1	Q8NGY0A0A126GWA4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR10X1	ENST00000623167.1 link	c.426C>T	p.Ile142Ile	synonymous_variant	Exon 1 of 1	6	NM_001004477.1	ENSP00000485609.1		Q8NGY0

Frequencies

GnomAD3 genomes

AF:

0.497

AC:

75368

AN:

151760

Hom.:

18924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.569

Gnomad AMI

AF:

0.410

Gnomad AMR

AF:

0.451

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.585

Gnomad SAS

AF:

0.444

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.457

Gnomad OTH

AF:

0.478

GnomAD3 exomes

AF:

0.474

AC:

119014

AN:

250940

Hom.:

28628

AF XY:

0.472

AC XY:

64026

AN XY:

135582

show subpopulations

Gnomad AFR exome

AF:

0.576

Gnomad AMR exome

AF:

0.414

Gnomad ASJ exome

AF:

0.478

Gnomad EAS exome

AF:

0.573

Gnomad SAS exome

AF:

0.436

Gnomad FIN exome

AF:

0.543

Gnomad NFE exome

AF:

0.459

Gnomad OTH exome

AF:

0.476

GnomAD4 exome

AF:

0.469

AC:

684929

AN:

1461632

Hom.:

161771

Cov.:

AF XY:

0.467

AC XY:

339704

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.574

Gnomad4 AMR exome

AF:

0.423

Gnomad4 ASJ exome

AF:

0.480

Gnomad4 EAS exome

AF:

0.582

Gnomad4 SAS exome

AF:

0.441

Gnomad4 FIN exome

AF:

0.539

Gnomad4 NFE exome

AF:

0.461

Gnomad4 OTH exome

AF:

0.479

GnomAD4 genome

AF:

0.497

AC:

75441

AN:

151880

Hom.:

18944

Cov.:

AF XY:

0.501

AC XY:

37193

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.569

Gnomad4 AMR

AF:

0.451

Gnomad4 ASJ

AF:

0.482

Gnomad4 EAS

AF:

0.585

Gnomad4 SAS

AF:

0.445

Gnomad4 FIN

AF:

0.532

Gnomad4 NFE

AF:

0.457

Gnomad4 OTH

AF:

0.482

Alfa

AF:

0.467

Hom.:

21392

Bravo

AF:

0.496

Asia WGS

AF:

0.536

AC:

1864

AN:

3478

EpiCase

AF:

0.455

EpiControl

AF:

0.454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.1

DANN

Benign

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over