1-247606123-G-A

Position:

• chr1-247606123-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001001914.1(OR2G3):​c.538G>A​(p.Glu180Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00562 in 1,614,134 control chromosomes in the GnomAD database, including 454 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (284 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (170 hom.)
• Consequence: OR2G3 NM_001001914.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.07

Genes affected

OR2G3 (HGNC:15008): (olfactory receptor family 2 subfamily G member 3) 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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019427538).
• BP6: Variant 1-247606123-G-A is Benign according to our data. Variant chr1-247606123-G-A is described in ClinVar as [Benign]. Clinvar id is 775701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2G3	NM_001001914.1	c.538G>A	p.Glu180Lys	missense_variant	1/1	ENST00000320002.3
LOC102724446	XR_426948.4	n.225+29732C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2G3	ENST00000320002.3	c.538G>A	p.Glu180Lys	missense_variant	1/1		NM_001001914.1	P1
	ENST00000435333.5	n.225+29732C>T		intron_variant, non_coding_transcript_variant		3
	ENST00000446347.1	n.437+29732C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 4756 AN: 152126 Hom.: 283 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0191

GnomAD3 exomes AF: 0.00819 AC: 2059 AN: 251402 Hom.: 93 AF XY: 0.00593 AC XY: 806 AN XY: 135874

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.00616

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00295 AC: 4312 AN: 1461890 Hom.: 170 Cov.: 34 AF XY: 0.00256 AC XY: 1863 AN XY: 727246

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.00731

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000121

Gnomad4 OTH exome AF: 0.00591

GnomAD4 genome AF: 0.0313 AC: 4764 AN: 152244 Hom.: 284 Cov.: 32 AF XY: 0.0302 AC XY: 2246 AN XY: 74430

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000624

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.00438 Hom.: 52

Bravo AF: 0.0351

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.109 AC: 479

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00964 AC: 1170

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0050	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.19
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.23
MVP		0.74
MPC		0.37
ClinPred		0.039	T
GERP RS		3.5
Varity_R		0.88
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs56795889; hg19: chr1-247769425; COSMIC: COSV60680708; COSMIC: COSV60680708;