NM_030876.6:c.68T>G

Variant names:

• chr6-29356128-A-C
• rs6930033
• NM_030876.6:c.68T>G

Variant summary

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

The NM_030876.6(OR5V1):​c.68T>G​(p.Leu23Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,611,594 control chromosomes in the GnomAD database, including 26,495 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2829 hom., cov: 32)
  • Exomes 𝑓: 0.17 (23666 hom.)
• Consequence: OR5V1 NM_030876.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 35 publications found

Genes affected

OR5V1 (HGNC:13972): (olfactory receptor family 5 subfamily V 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. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005331278).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030876.6. 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
	OR5V1	NM_030876.6	MANE Select	c.68T>G	p.Leu23Trp	missense	Exon 2 of 2	NP_110503.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5V1	ENST00000641768.1	MANE Select	c.68T>G	p.Leu23Trp	missense	Exon 2 of 2	ENSP00000493269.1
	OR5V1	ENST00000377154.1	TSL:6	c.68T>G	p.Leu23Trp	missense	Exon 4 of 4	ENSP00000366359.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27757 AN: 151982 Hom.: 2832 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.190

GnomAD2 exomes AF: 0.213 AC: 52772 AN: 247854 AF XY: 0.213

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.282

Gnomad ASJ exome AF: 0.223

Gnomad EAS exome AF: 0.435

Gnomad FIN exome AF: 0.174

Gnomad NFE exome AF: 0.154

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.169 AC: 246934 AN: 1459494 Hom.: 23666 Cov.: 35 AF XY: 0.173 AC XY: 125321 AN XY: 725994

African (AFR) AF: 0.158 AC: 5281 AN: 33340

American (AMR) AF: 0.277 AC: 12286 AN: 44286

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 5696 AN: 25974

East Asian (EAS) AF: 0.396 AC: 15719 AN: 39684

South Asian (SAS) AF: 0.270 AC: 23158 AN: 85708

European-Finnish (FIN) AF: 0.176 AC: 9375 AN: 53322

Middle Eastern (MID) AF: 0.261 AC: 1501 AN: 5742

European-Non Finnish (NFE) AF: 0.146 AC: 162521 AN: 1111162

Other (OTH) AF: 0.189 AC: 11397 AN: 60276

GnomAD4 genome AF: 0.182 AC: 27753 AN: 152100 Hom.: 2829 Cov.: 32 AF XY: 0.189 AC XY: 14090 AN XY: 74376

African (AFR) AF: 0.160 AC: 6657 AN: 41502

American (AMR) AF: 0.247 AC: 3766 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 751 AN: 3470

East Asian (EAS) AF: 0.416 AC: 2138 AN: 5140

South Asian (SAS) AF: 0.308 AC: 1486 AN: 4824

European-Finnish (FIN) AF: 0.170 AC: 1801 AN: 10604

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10459 AN: 67976

Other (OTH) AF: 0.190 AC: 402 AN: 2114

Alfa AF: 0.173 Hom.: 7813

Bravo AF: 0.186

TwinsUK AF: 0.142 AC: 525

ALSPAC AF: 0.142 AC: 549

ESP6500AA AF: 0.148 AC: 651

ESP6500EA AF: 0.160 AC: 1376

ExAC AF: 0.208 AC: 25214

Asia WGS AF: 0.325 AC: 1128 AN: 3478

EpiCase AF: 0.163

EpiControl AF: 0.162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.033	T
Eigen	Benign	0.10
Eigen_PC	Benign	-0.063
FATHMM_MKL	Benign	0.16	N
MetaRNN	Benign	0.0053	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.3
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.092
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.14
MPC		0.49
ClinPred		0.028	T
GERP RS		4.4
Varity_R		0.14
gMVP		0.32
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6930033; hg19: chr6-29323905; COSMIC: COSV65829551;