NM_002551.5:c.-279+25217G>T

Variant names:

• chr17-3310812-C-A
• rs9911226
• NM_002551.5:c.-279+25217G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002551.5(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 NM_002551.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 14 publications found

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]

ENSG00000290820 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002551.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR3A2	NM_002551.5	MANE Select	c.-279+25217G>T		intron	N/A	NP_002542.4
	OR3A4P	NR_024128.1		n.568C>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR3A2	ENST00000573901.3	TSL:3 MANE Select	c.-279+25217G>T		intron	N/A	ENSP00000516654.1
	OR3A4P	ENST00000323164.7	TSL:6	n.502C>A		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000290820	ENST00000624752.1	TSL:6	n.827C>A		non_coding_transcript_exon	Exon 1 of 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

GnomAD2 exomes AF: 0.125 AC: 31456 AN: 251436 AF XY: 0.119

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 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

African (AFR) AF: 0.364 AC: 4916 AN: 13518

American (AMR) AF: 0.161 AC: 5984 AN: 37186

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 1883 AN: 14142

East Asian (EAS) AF: 0.0290 AC: 492 AN: 16990

South Asian (SAS) AF: 0.113 AC: 8151 AN: 72234

European-Finnish (FIN) AF: 0.0621 AC: 2095 AN: 33748

Middle Eastern (MID) AF: 0.122 AC: 420 AN: 3450

European-Non Finnish (NFE) AF: 0.0611 AC: 26789 AN: 438268

Other (OTH) AF: 0.0912 AC: 2399 AN: 26294

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

African (AFR) AF: 0.405 AC: 16800 AN: 41456

American (AMR) AF: 0.177 AC: 2710 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 516 AN: 3472

East Asian (EAS) AF: 0.0401 AC: 207 AN: 5160

South Asian (SAS) AF: 0.115 AC: 554 AN: 4820

European-Finnish (FIN) AF: 0.0623 AC: 661 AN: 10614

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0950 AC: 6459 AN: 68002

Other (OTH) AF: 0.187 AC: 394 AN: 2108

Alfa AF: 0.141 Hom.: 4904

Bravo AF: 0.204

Asia WGS AF: 0.114 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.34
PhyloP100		-2.3

Splicing

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

Other links and lift over

dbSNP: rs9911226; hg19: chr17-3214106;