NM_001001953.1:c.417A>G

Variant names:

• chr11-124023429-A-G
• rs28499345
• NM_001001953.1:c.417A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001001953.1(OR10G9):​c.417A>G​(p.Arg139Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 1,576,828 control chromosomes in the GnomAD database, including 593,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (57065 hom., cov: 24)
  • Exomes 𝑓: 0.86 (536868 hom.)
• Consequence: OR10G9 NM_001001953.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.81
• Publications: 8 publications found

Genes affected

OR10G9 (HGNC:15129): (olfactory receptor family 10 subfamily G member 9) 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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 11-124023429-A-G is Benign according to our data. Variant chr11-124023429-A-G is described in ClinVar as Benign. ClinVar VariationId is 768493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.81 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001953.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10G9	NM_001001953.1	MANE Select	c.417A>G	p.Arg139Arg	synonymous	Exon 1 of 1	NP_001001953.1	Q8NGN4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10G9	ENST00000375024.1	TSL:6 MANE Select	c.417A>G	p.Arg139Arg	synonymous	Exon 1 of 1	ENSP00000364164.1	Q8NGN4

Frequencies

GnomAD3 genomes AF: 0.872 AC: 130390 AN: 149514 Hom.: 57016 Cov.: 24

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.861

Gnomad OTH AF: 0.863

GnomAD2 exomes AF: 0.864 AC: 206889 AN: 239402 AF XY: 0.855

Gnomad AFR exome AF: 0.918

Gnomad AMR exome AF: 0.923

Gnomad ASJ exome AF: 0.891

Gnomad EAS exome AF: 0.815

Gnomad FIN exome AF: 0.916

Gnomad NFE exome AF: 0.877

Gnomad OTH exome AF: 0.863

GnomAD4 exome AF: 0.864 AC: 1233576 AN: 1427198 Hom.: 536868 Cov.: 61 AF XY: 0.859 AC XY: 610262 AN XY: 710698

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.917 AC: 30284 AN: 33038

American (AMR) AF: 0.907 AC: 40339 AN: 44480

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 22755 AN: 25878

East Asian (EAS) AF: 0.831 AC: 32771 AN: 39426

South Asian (SAS) AF: 0.696 AC: 58831 AN: 84484

European-Finnish (FIN) AF: 0.898 AC: 46731 AN: 52022

Middle Eastern (MID) AF: 0.836 AC: 4761 AN: 5696

European-Non Finnish (NFE) AF: 0.874 AC: 946000 AN: 1082958

Other (OTH) AF: 0.863 AC: 51104 AN: 59216

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.872 AC: 130494 AN: 149630 Hom.: 57065 Cov.: 24 AF XY: 0.871 AC XY: 63568 AN XY: 72952

African (AFR) AF: 0.909 AC: 36796 AN: 40482

American (AMR) AF: 0.892 AC: 13350 AN: 14960

Ashkenazi Jewish (ASJ) AF: 0.881 AC: 3038 AN: 3450

East Asian (EAS) AF: 0.791 AC: 4007 AN: 5064

South Asian (SAS) AF: 0.688 AC: 3170 AN: 4610

European-Finnish (FIN) AF: 0.888 AC: 9178 AN: 10330

Middle Eastern (MID) AF: 0.870 AC: 254 AN: 292

European-Non Finnish (NFE) AF: 0.861 AC: 58128 AN: 67484

Other (OTH) AF: 0.856 AC: 1759 AN: 2056

Alfa AF: 0.865 Hom.: 10326

Bravo AF: 0.879

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.35
DANN	Benign	0.33
PhyloP100		-3.8
PromoterAI		0.0095	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs28499345; hg19: chr11-123894136; COSMIC: COSV66686424; COSMIC: COSV66686424;