rs1217872034

Variant names:

• chr11-48264189-C-A
• rs1217872034
• NM_001004726.1:c.329C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-48264189-C-A
• chr11-48264189-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004726.1(OR4X1):​c.329C>A​(p.Ala110Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: OR4X1 NM_001004726.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.318
• Publications: 1 publications found

Genes affected

OR4X1 (HGNC:14854): (olfactory receptor family 4 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, Jul 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10255259).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004726.1. 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
	OR4X1	NM_001004726.1	MANE Select	c.329C>A	p.Ala110Asp	missense	Exon 1 of 1	NP_001004726.1	Q8NH49

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4X1	ENST00000320048.1	TSL:6 MANE Select	c.329C>A	p.Ala110Asp	missense	Exon 1 of 1	ENSP00000321506.1	Q8NH49

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250912 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461812 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 727202

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111966

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.49	N
PhyloP100		-0.32
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.052
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.29	B
Vest4		0.26
MutPred		0.57		Gain of phosphorylation at T108 (P = 0.1935)
MVP		0.40
MPC		0.0019
ClinPred		0.15	T
GERP RS		3.1
PromoterAI		-0.049	Neutral
Varity_R		0.47
gMVP		0.32
Mutation Taster		=100/0	polymorphism

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: rs1217872034; hg19: chr11-48285741;