17-3310812-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002551.5(OR3A2):​c.-279+25217G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000152 in 657,500 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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>C		intron	N/A	NP_002542.4
	OR3A4P	NR_024128.1		n.568C>G		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>C		intron	N/A	ENSP00000516654.1
	OR3A4P	ENST00000323164.7	TSL:6	n.502C>G		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000290820	ENST00000624752.1	TSL:6	n.827C>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251436 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 0.00000152 AC: 1 AN: 657500 Hom.: 0 Cov.: 9 AF XY: 0.00000286 AC XY: 1 AN XY: 349276

African (AFR) AF: 0.00 AC: 0 AN: 13598

American (AMR) AF: 0.0000269 AC: 1 AN: 37192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14162

East Asian (EAS) AF: 0.00 AC: 0 AN: 16998

South Asian (SAS) AF: 0.00 AC: 0 AN: 72264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3456

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 439674

Other (OTH) AF: 0.00 AC: 0 AN: 26398

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.19
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;