6-29356128-A-C

Position:

• chr6-29356128-A-C

Variant summary

Our verdict is Benign. Variant got -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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5V1	NM_030876.6	c.68T>G	p.Leu23Trp	missense_variant	2/2	ENST00000641768.1	NP_110503.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR5V1	ENST00000641768.1	c.68T>G	p.Leu23Trp	missense_variant	2/2		NM_030876.6	ENSP00000493269.1
OR5V1	ENST00000377154.1	c.68T>G	p.Leu23Trp	missense_variant	4/4	6		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

GnomAD3 exomes AF: 0.213 AC: 52772 AN: 247854 Hom.: 6680 AF XY: 0.213 AC XY: 28565 AN XY: 134268

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 SAS exome AF: 0.272

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

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.396

Gnomad4 SAS exome AF: 0.270

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.189

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

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.190

Alfa AF: 0.172 Hom.: 4976

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 v4.3

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;T;T
Eigen	Benign	0.10
Eigen_PC	Benign	-0.063
FATHMM_MKL	Benign	0.16	N
MetaRNN	Benign	0.0053	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M;M
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.7	.;D;D
REVEL	Benign	0.092
Sift	Uncertain	0.018	.;D;D
Sift4G	Uncertain	0.0080	.;D;D
Polyphen		1.0	D;D;D
Vest4		0.14
MPC		0.49
ClinPred		0.028	T
GERP RS		4.4
Varity_R		0.14
gMVP		0.32

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

Publications

LitVar

Other links and lift over

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