rs2427808

chr1-158607377-A-T

Variant summary

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

The NM_001004478.2(OR10Z1):c.939A>T(p.Gly313=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,609,288 control chromosomes in the GnomAD database, including 12,861 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 0.10 (875 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11986 hom.)
• Consequence: OR10Z1 NM_001004478.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600

Genes affected

OR10Z1 (HGNC:14996): (olfactory receptor family 10 subfamily Z 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=-0.006 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR10Z1	NM_001004478.2	c.939A>T	p.Gly313=	synonymous_variant	2/2	ENST00000641002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10Z1	ENST00000641002.1	c.939A>T	p.Gly313=	synonymous_variant	2/2		NM_001004478.2	P1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15788 AN: 152072 Hom.: 871 Cov.: 32

Gnomad AFR AF: 0.0642

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0686

Gnomad EAS AF: 0.0895

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.0707

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.105

GnomAD3 exomes AF: 0.120 AC: 29754 AN: 248258 Hom.: 2038 AF XY: 0.126 AC XY: 16831 AN XY: 134006

Gnomad AFR exome AF: 0.0670

Gnomad AMR exome AF: 0.0993

Gnomad ASJ exome AF: 0.0728

Gnomad EAS exome AF: 0.0872

Gnomad SAS exome AF: 0.206

Gnomad FIN exome AF: 0.0686

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.125 AC: 181836 AN: 1457098 Hom.: 11986 Cov.: 30 AF XY: 0.128 AC XY: 92638 AN XY: 724870

Gnomad4 AFR exome AF: 0.0651

Gnomad4 AMR exome AF: 0.0993

Gnomad4 ASJ exome AF: 0.0719

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.206

Gnomad4 FIN exome AF: 0.0738

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.104 AC: 15802 AN: 152190 Hom.: 875 Cov.: 32 AF XY: 0.103 AC XY: 7630 AN XY: 74400

Gnomad4 AFR AF: 0.0642

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0686

Gnomad4 EAS AF: 0.0893

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.0707

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.105

Alfa AF: 0.113 Hom.: 338

Bravo AF: 0.102

Asia WGS AF: 0.137 AC: 477 AN: 3478

EpiCase AF: 0.123

EpiControl AF: 0.127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	3.4
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2427808; hg19: chr1-158577167; COSMIC: COSV63524599; COSMIC: COSV63524599;