11-48263749-A-G

Variant names:

• chr11-48263749-A-G
• rs713325
• NM_001004726.1:c.-112A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004726.1(OR4X1):​c.-112A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 778,014 control chromosomes in the GnomAD database, including 201,722 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 0.67 (35696 hom., cov: 32)
  • Exomes 𝑓: 0.72 (166026 hom.)
• Consequence: OR4X1 NM_001004726.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4X1	NM_001004726.1	c.-112A>G		upstream_gene_variant		ENST00000320048.1	NP_001004726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4X1	ENST00000320048.1	c.-112A>G		upstream_gene_variant		6	NM_001004726.1	ENSP00000321506.1

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102497 AN: 151976 Hom.: 35686 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.835

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.669

GnomAD4 exome AF: 0.723 AC: 452514 AN: 625920 Hom.: 166026 AF XY: 0.716 AC XY: 233471 AN XY: 326252

Gnomad4 AFR exome AF: 0.501

Gnomad4 AMR exome AF: 0.775

Gnomad4 ASJ exome AF: 0.691

Gnomad4 EAS exome AF: 0.635

Gnomad4 SAS exome AF: 0.541

Gnomad4 FIN exome AF: 0.794

Gnomad4 NFE exome AF: 0.756

Gnomad4 OTH exome AF: 0.696

GnomAD4 genome AF: 0.674 AC: 102544 AN: 152094 Hom.: 35696 Cov.: 32 AF XY: 0.674 AC XY: 50094 AN XY: 74348

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.578

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.811

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.670

Alfa AF: 0.711 Hom.: 5924

Bravo AF: 0.665

Asia WGS AF: 0.510 AC: 1773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.0
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs713325; hg19: chr11-48285301;