rs863360

chr1-158579474-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001004477.1(OR10X1):c.426C>T(p.Ile142=) 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

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

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/exons	MANE	UniProt
OR10X1	NM_001004477.1	c.426C>T	p.Ile142=	synonymous_variant	1/1	ENST00000623167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10X1	ENST00000623167.1	c.426C>T	p.Ile142=	synonymous_variant	1/1		NM_001004477.1	P1

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

GnomAD3 exomes AF: 0.474 AC: 119014 AN: 250940 Hom.: 28628 AF XY: 0.472 AC XY: 64026 AN XY: 135582

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

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.: 30 AF XY: 0.501 AC XY: 37193 AN XY: 74218

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

Other links and lift over

dbSNP: rs863360; hg19: chr1-158549264; COSMIC: COSV63767036;