NM_002551.5:c.-278-167G>C

Variant names:

• chr17-3284718-C-G
• rs2005290
• NM_002551.5:c.-278-167G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002551.5(OR3A2):​c.-278-167G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0465 in 117,604 control chromosomes in the GnomAD database, including 520 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 0.046 (520 hom., cov: 28)
• Consequence: OR3A2 NM_002551.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS2: High Homozygotes in GnomAd4 at 520 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR3A2	NM_002551.5	c.-278-167G>C		intron_variant	Intron 2 of 4	ENST00000573901.3	NP_002542.4
OR3A2	XM_047436157.1	c.-254-167G>C		intron_variant	Intron 4 of 6		XP_047292113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR3A2	ENST00000573901.3	c.-278-167G>C		intron_variant	Intron 2 of 4	3	NM_002551.5	ENSP00000516654.1
OR3A2	ENST00000573491.5	c.-84-5565G>C		intron_variant	Intron 3 of 4	3		ENSP00000493118.1
OR3A2	ENST00000576166.2	c.-84-5565G>C		intron_variant	Intron 2 of 3	5		ENSP00000493095.1

Frequencies

GnomAD3 genomes AF: 0.0465 AC: 5470 AN: 117546 Hom.: 522 Cov.: 28

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0486

Gnomad ASJ AF: 0.0325

Gnomad EAS AF: 0.0146

Gnomad SAS AF: 0.0777

Gnomad FIN AF: 0.0144

Gnomad MID AF: 0.0805

Gnomad NFE AF: 0.0176

Gnomad OTH AF: 0.0416

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0465 AC: 5464 AN: 117604 Hom.: 520 Cov.: 28 AF XY: 0.0453 AC XY: 2597 AN XY: 57344

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.123 AC: 3287 AN: 26806

American (AMR) AF: 0.0490 AC: 540 AN: 11030

Ashkenazi Jewish (ASJ) AF: 0.0325 AC: 89 AN: 2740

East Asian (EAS) AF: 0.0146 AC: 68 AN: 4658

South Asian (SAS) AF: 0.0764 AC: 247 AN: 3232

European-Finnish (FIN) AF: 0.0144 AC: 128 AN: 8874

Middle Eastern (MID) AF: 0.0682 AC: 15 AN: 220

European-Non Finnish (NFE) AF: 0.0176 AC: 1014 AN: 57644

Other (OTH) AF: 0.0419 AC: 66 AN: 1574

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0123 Hom.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.47
PhyloP100		-0.12
PromoterAI		0.058	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs2005290; hg19: chr17-3188012; COSMIC: COSV73801387;