rs863360

Variant names:

• chr1-158579474-G-A
• rs863360
• NM_001004477.1:c.426C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251
• Publications: 20 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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	c.426C>T	p.Ile142Ile	synonymous_variant	Exon 1 of 1	ENST00000623167.1	NP_001004477.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75368 AN: 151760 Hom.: 18924 Cov.: 30

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

GnomAD2 exomes AF: 0.474 AC: 119014 AN: 250940 AF XY: 0.472

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 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.: 44 AF XY: 0.467 AC XY: 339704 AN XY: 727100

African (AFR) AF: 0.574 AC: 19208 AN: 33478

American (AMR) AF: 0.423 AC: 18898 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 12526 AN: 26120

East Asian (EAS) AF: 0.582 AC: 23084 AN: 39690

South Asian (SAS) AF: 0.441 AC: 38027 AN: 86246

European-Finnish (FIN) AF: 0.539 AC: 28788 AN: 53414

Middle Eastern (MID) AF: 0.458 AC: 2640 AN: 5766

European-Non Finnish (NFE) AF: 0.461 AC: 512803 AN: 1111822

Other (OTH) AF: 0.479 AC: 28955 AN: 60386

GnomAD4 genome AF: 0.497 AC: 75441 AN: 151880 Hom.: 18944 Cov.: 30 AF XY: 0.501 AC XY: 37193 AN XY: 74218

African (AFR) AF: 0.569 AC: 23545 AN: 41390

American (AMR) AF: 0.451 AC: 6891 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1674 AN: 3470

East Asian (EAS) AF: 0.585 AC: 3012 AN: 5152

South Asian (SAS) AF: 0.445 AC: 2145 AN: 4818

European-Finnish (FIN) AF: 0.532 AC: 5612 AN: 10542

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31038 AN: 67930

Other (OTH) AF: 0.482 AC: 1018 AN: 2110

Alfa AF: 0.470 Hom.: 26863

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
PhyloP100		0.25
PromoterAI		-0.00040	Neutral
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: rs863360; hg19: chr1-158549264; COSMIC: COSV63767036;