6-29356061-A-C

Position:

• chr6-29356061-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.135T>G​(p.Ile45Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 1,613,862 control chromosomes in the GnomAD database, including 451 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 0.018 (36 hom., cov: 32)
  • Exomes 𝑓: 0.022 (415 hom.)
• Consequence: OR5V1 NM_030876.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50

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=0.0038072765).
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR5V1	NM_030876.6	c.135T>G	p.Ile45Met	missense_variant	2/2	ENST00000641768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR5V1	ENST00000641768.1	c.135T>G	p.Ile45Met	missense_variant	2/2		NM_030876.6	P1
OR5V1	ENST00000377154.1	c.135T>G	p.Ile45Met	missense_variant	4/4			P1

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2774 AN: 152034 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.00570

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.0234

Gnomad EAS AF: 0.0326

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0236

Gnomad OTH AF: 0.0172

GnomAD3 exomes AF: 0.0201 AC: 5044 AN: 250920 Hom.: 80 AF XY: 0.0208 AC XY: 2823 AN XY: 135648

Gnomad AFR exome AF: 0.00572

Gnomad AMR exome AF: 0.0118

Gnomad ASJ exome AF: 0.0199

Gnomad EAS exome AF: 0.0183

Gnomad SAS exome AF: 0.0174

Gnomad FIN exome AF: 0.0269

Gnomad NFE exome AF: 0.0244

Gnomad OTH exome AF: 0.0201

GnomAD4 exome AF: 0.0222 AC: 32496 AN: 1461710 Hom.: 415 Cov.: 36 AF XY: 0.0224 AC XY: 16310 AN XY: 727136

Gnomad4 AFR exome AF: 0.00681

Gnomad4 AMR exome AF: 0.0119

Gnomad4 ASJ exome AF: 0.0210

Gnomad4 EAS exome AF: 0.0525

Gnomad4 SAS exome AF: 0.0189

Gnomad4 FIN exome AF: 0.0263

Gnomad4 NFE exome AF: 0.0221

Gnomad4 OTH exome AF: 0.0211

GnomAD4 genome AF: 0.0183 AC: 2777 AN: 152152 Hom.: 36 Cov.: 32 AF XY: 0.0182 AC XY: 1355 AN XY: 74404

Gnomad4 AFR AF: 0.00581

Gnomad4 AMR AF: 0.0155

Gnomad4 ASJ AF: 0.0234

Gnomad4 EAS AF: 0.0327

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.0238

Gnomad4 NFE AF: 0.0235

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0213 Hom.: 84

Bravo AF: 0.0160

TwinsUK AF: 0.0248 AC: 92

ALSPAC AF: 0.0213 AC: 82

ESP6500AA AF: 0.00681 AC: 30

ESP6500EA AF: 0.0245 AC: 211

ExAC AF: 0.0207 AC: 2518

Asia WGS AF: 0.0230 AC: 79 AN: 3478

EpiCase AF: 0.0207

EpiControl AF: 0.0245

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0058	T;T;T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.0086	N
MetaRNN	Benign	0.0038	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.1	M;M;M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.3	.;N;N
REVEL	Benign	0.061
Sift	Benign	0.035	.;D;D
Sift4G	Benign	0.25	.;T;T
Polyphen		0.93	P;P;P
Vest4		0.094
MPC		0.28
ClinPred		0.039	T
GERP RS		-3.2
Varity_R		0.11
gMVP		0.25

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: rs9257770; hg19: chr6-29323838; COSMIC: COSV65828639;