rs1151640

Variant names:

• chr1-247672648-T-C
• rs1151640
• NM_001005487.2:c.394A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001005487.2(OR13G1):​c.394A>G​(p.Ile132Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,613,520 control chromosomes in the GnomAD database, including 155,796 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.37 (11792 hom., cov: 32)
  • Exomes 𝑓: 0.44 (144004 hom.)
• Consequence: OR13G1 NM_001005487.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155

Genes affected

OR13G1 (HGNC:14999): (olfactory receptor family 13 subfamily G 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]

ENSG00000235749 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.544733E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR13G1	NM_001005487.2	c.394A>G	p.Ile132Val	missense_variant	Exon 2 of 2	ENST00000642119.1	NP_001005487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR13G1	ENST00000642119.1	c.394A>G	p.Ile132Val	missense_variant	Exon 2 of 2		NM_001005487.2	ENSP00000493110.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56268 AN: 151792 Hom.: 11781 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.368

GnomAD3 exomes AF: 0.458 AC: 114803 AN: 250916 Hom.: 28215 AF XY: 0.453 AC XY: 61470 AN XY: 135582

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.666

Gnomad ASJ exome AF: 0.421

Gnomad EAS exome AF: 0.599

Gnomad SAS exome AF: 0.435

Gnomad FIN exome AF: 0.410

Gnomad NFE exome AF: 0.433

Gnomad OTH exome AF: 0.445

GnomAD4 exome AF: 0.438 AC: 640088 AN: 1461612 Hom.: 144004 Cov.: 58 AF XY: 0.438 AC XY: 318168 AN XY: 727092

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.653

Gnomad4 ASJ exome AF: 0.423

Gnomad4 EAS exome AF: 0.621

Gnomad4 SAS exome AF: 0.435

Gnomad4 FIN exome AF: 0.414

Gnomad4 NFE exome AF: 0.434

Gnomad4 OTH exome AF: 0.423

GnomAD4 genome AF: 0.371 AC: 56291 AN: 151908 Hom.: 11792 Cov.: 32 AF XY: 0.374 AC XY: 27767 AN XY: 74240

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.373

Alfa AF: 0.424 Hom.: 30441

Bravo AF: 0.376

TwinsUK AF: 0.436 AC: 1616

ALSPAC AF: 0.449 AC: 1729

ESP6500AA AF: 0.168 AC: 739

ESP6500EA AF: 0.425 AC: 3654

ExAC AF: 0.445 AC: 54006

Asia WGS AF: 0.507 AC: 1758 AN: 3478

EpiCase AF: 0.420

EpiControl AF: 0.425

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.5
DANN	Benign	0.74
DEOGEN2	Benign	0.0060	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.13	.;T
MetaRNN	Benign	0.0000055	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.32	.;N
REVEL	Benign	0.022
Sift	Benign	0.21	.;T
Sift4G	Benign	0.31	.;T
Polyphen		0.0020	B;B
Vest4		0.017
MPC		0.12
ClinPred		0.0082	T
GERP RS		-3.4
Varity_R		0.10
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1151640; hg19: chr1-247835950; COSMIC: COSV62943381; COSMIC: COSV62943381;