rs769423

chr17-3092923-C-T

Variant summary

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

The NM_002548.3(OR1D2):c.74G>A(p.Arg25Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0719 in 1,613,724 control chromosomes in the GnomAD database, including 4,762 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 0.087 (731 hom., cov: 31)
  • Exomes 𝑓: 0.070 (4031 hom.)
• Consequence: OR1D2 NM_002548.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.56

Genes affected

OR1D2 (HGNC:8183): (olfactory receptor family 1 subfamily D member 2) 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=0.0015032887).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR1D2	NM_002548.3	c.74G>A	p.Arg25Gln	missense_variant	2/2	ENST00000641833.1
OR1D2	NM_001386088.1	c.74G>A	p.Arg25Gln	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR1D2	ENST00000641833.1	c.74G>A	p.Arg25Gln	missense_variant	2/2		NM_002548.3	P1
OR1D2	ENST00000641064.1	c.74G>A	p.Arg25Gln	missense_variant	2/2			P1

Frequencies

GnomAD3 genomes AF: 0.0869 AC: 13197 AN: 151786 Hom.: 729 Cov.: 31

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.0505

Gnomad ASJ AF: 0.0666

Gnomad EAS AF: 0.00618

Gnomad SAS AF: 0.0855

Gnomad FIN AF: 0.0376

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0715

Gnomad OTH AF: 0.0873

GnomAD3 exomes AF: 0.0672 AC: 16899 AN: 251366 Hom.: 752 AF XY: 0.0692 AC XY: 9403 AN XY: 135852

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.0294

Gnomad ASJ exome AF: 0.0643

Gnomad EAS exome AF: 0.00734

Gnomad SAS exome AF: 0.0891

Gnomad FIN exome AF: 0.0368

Gnomad NFE exome AF: 0.0760

Gnomad OTH exome AF: 0.0634

GnomAD4 exome AF: 0.0703 AC: 102782 AN: 1461820 Hom.: 4031 Cov.: 33 AF XY: 0.0712 AC XY: 51814 AN XY: 727214

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.0324

Gnomad4 ASJ exome AF: 0.0621

Gnomad4 EAS exome AF: 0.00290

Gnomad4 SAS exome AF: 0.0910

Gnomad4 FIN exome AF: 0.0416

Gnomad4 NFE exome AF: 0.0711

Gnomad4 OTH exome AF: 0.0730

GnomAD4 genome AF: 0.0870 AC: 13218 AN: 151904 Hom.: 731 Cov.: 31 AF XY: 0.0843 AC XY: 6258 AN XY: 74242

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.0505

Gnomad4 ASJ AF: 0.0666

Gnomad4 EAS AF: 0.00619

Gnomad4 SAS AF: 0.0858

Gnomad4 FIN AF: 0.0376

Gnomad4 NFE AF: 0.0715

Gnomad4 OTH AF: 0.0859

Alfa AF: 0.0807 Hom.: 270

Bravo AF: 0.0910

TwinsUK AF: 0.0680 AC: 252

ALSPAC AF: 0.0623 AC: 240

ESP6500AA AF: 0.147 AC: 649

ESP6500EA AF: 0.0697 AC: 599

ExAC AF: 0.0735 AC: 8919

Asia WGS AF: 0.0500 AC: 172 AN: 3478

EpiCase AF: 0.0683

EpiControl AF: 0.0706

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.0060
Dann	Benign	0.28
DEOGEN2	Benign	0.0037	T;T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.014	N
MetaRNN	Benign	0.0015	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.83	N;N;N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.17	T
Polyphen		0.0010	B;B;B
Vest4		0.031
MPC		0.088
ClinPred		0.0024	T
GERP RS		-6.8
Varity_R		0.023
gMVP		0.26

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: rs769423; hg19: chr17-2996217; COSMIC: COSV58921320;