rs9911226

Positions:

• chr17-3310812-C-A
• chr17-3310812-C-G

Variant summary

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

The ENST00000573901.3(OR3A2):​c.-279+25217G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 807,956 control chromosomes in the GnomAD database, including 7,671 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 0.19 (4143 hom., cov: 32)
  • Exomes 𝑓: 0.081 (3528 hom.)
• Consequence: OR3A2 ENST00000573901.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29

Genes affected

OR3A2 (HGNC:8283): (olfactory receptor family 3 subfamily A member 2) 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]

OR3A4P (HGNC:15510): (olfactory receptor family 3 subfamily A member 4 pseudogene) 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 transcribed and contains an intact ORF, but it is predicted to be a pseudogene due to a poorly conserved 7-transmembrane domain structure. [provided by RefSeq, Sep 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR3A2	NM_002551.5	c.-279+25217G>T		intron_variant		ENST00000573901.3	NP_002542.4
OR3A2	XM_047436157.1	c.-528-10966G>T		intron_variant			XP_047292113.1
OR3A4P	NR_024128.1	n.568C>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR3A2	ENST00000573901.3	c.-279+25217G>T		intron_variant		3	NM_002551.5	ENSP00000516654	P1
OR3A4P	ENST00000323164.7	n.502C>A		non_coding_transcript_exon_variant	1/1
	ENST00000624752.1	n.827C>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28386 AN: 152008 Hom.: 4124 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0400

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0623

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0950

Gnomad OTH AF: 0.182

GnomAD3 exomes AF: 0.125 AC: 31456 AN: 251436 Hom.: 2921 AF XY: 0.119 AC XY: 16168 AN XY: 135900

Gnomad AFR exome AF: 0.413

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.150

Gnomad EAS exome AF: 0.0419

Gnomad SAS exome AF: 0.122

Gnomad FIN exome AF: 0.0611

Gnomad NFE exome AF: 0.0974

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.0810 AC: 53129 AN: 655830 Hom.: 3528 Cov.: 9 AF XY: 0.0832 AC XY: 28993 AN XY: 348446

Gnomad4 AFR exome AF: 0.364

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.133

Gnomad4 EAS exome AF: 0.0290

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.0621

Gnomad4 NFE exome AF: 0.0611

Gnomad4 OTH exome AF: 0.0912

GnomAD4 genome AF: 0.187 AC: 28448 AN: 152126 Hom.: 4143 Cov.: 32 AF XY: 0.182 AC XY: 13556 AN XY: 74392

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.0401

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0623

Gnomad4 NFE AF: 0.0950

Gnomad4 OTH AF: 0.187

Alfa AF: 0.124 Hom.: 2782

Bravo AF: 0.204

Asia WGS AF: 0.114 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9911226; hg19: chr17-3214106;