chr6-29356061-A-C

Variant names:

• chr6-29356061-A-C
• rs9257770
• NM_030876.6:c.135T>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.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. 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 0.018 (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
• Publications: 21 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=0.0038072765).
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0506 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.135T>G	p.Ile45Met	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.135T>G	p.Ile45Met	missense	Exon 2 of 2	ENSP00000493269.1
	OR5V1	ENST00000377154.1	TSL:6	c.135T>G	p.Ile45Met	missense	Exon 4 of 4	ENSP00000366359.1

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

GnomAD2 exomes AF: 0.0201 AC: 5044 AN: 250920 AF XY: 0.0208

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 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

African (AFR) AF: 0.00681 AC: 228 AN: 33474

American (AMR) AF: 0.0119 AC: 532 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 548 AN: 26126

East Asian (EAS) AF: 0.0525 AC: 2083 AN: 39696

South Asian (SAS) AF: 0.0189 AC: 1626 AN: 86248

European-Finnish (FIN) AF: 0.0263 AC: 1404 AN: 53414

Middle Eastern (MID) AF: 0.0322 AC: 186 AN: 5768

European-Non Finnish (NFE) AF: 0.0221 AC: 24615 AN: 1111884

Other (OTH) AF: 0.0211 AC: 1274 AN: 60384

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

African (AFR) AF: 0.00581 AC: 241 AN: 41512

American (AMR) AF: 0.0155 AC: 237 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0234 AC: 81 AN: 3466

East Asian (EAS) AF: 0.0327 AC: 169 AN: 5174

South Asian (SAS) AF: 0.0178 AC: 86 AN: 4824

European-Finnish (FIN) AF: 0.0238 AC: 252 AN: 10608

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0235 AC: 1600 AN: 67966

Other (OTH) AF: 0.0170 AC: 36 AN: 2112

Alfa AF: 0.0210 Hom.: 164

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 v4.9

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
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.0086	N
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-2.5
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.061
Sift	Benign	0.035	D
Sift4G	Benign	0.25	T
Polyphen		0.93	P
Vest4		0.094
MPC		0.28
ClinPred		0.039	T
GERP RS		-3.2
Varity_R		0.11
gMVP		0.25
Mutation Taster		=99/1	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: rs9257770; hg19: chr6-29323838; COSMIC: COSV65828639;