chr1-247605646-C-T

Position:

• chr1-247605646-C-T

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.61C>T​(p.Pro21Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00457 in 1,613,942 control chromosomes in the GnomAD database, including 319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (175 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (144 hom.)
• Consequence: OR2G3 NM_001001914.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.10

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=0.0024614334).
• BP6: Variant 1-247605646-C-T is Benign according to our data. Variant chr1-247605646-C-T is described in ClinVar as [Benign]. Clinvar id is 778815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2G3	NM_001001914.1	c.61C>T	p.Pro21Ser	missense_variant	1/1	ENST00000320002.3
LOC102724446	XR_426948.4	n.225+30209G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2G3	ENST00000320002.3	c.61C>T	p.Pro21Ser	missense_variant	1/1		NM_001001914.1	P1
	ENST00000435333.5	n.225+30209G>A		intron_variant, non_coding_transcript_variant		3
	ENST00000446347.1	n.437+30209G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0245 AC: 3732 AN: 152142 Hom.: 175 Cov.: 32

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0191

GnomAD3 exomes AF: 0.00632 AC: 1587 AN: 251028 Hom.: 58 AF XY: 0.00448 AC XY: 607 AN XY: 135632

Gnomad AFR exome AF: 0.0860

Gnomad AMR exome AF: 0.00422

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00249 AC: 3639 AN: 1461684 Hom.: 144 Cov.: 31 AF XY: 0.00210 AC XY: 1526 AN XY: 727154

Gnomad4 AFR exome AF: 0.0891

Gnomad4 AMR exome AF: 0.00461

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000278

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000926

Gnomad4 OTH exome AF: 0.00507

GnomAD4 genome AF: 0.0245 AC: 3733 AN: 152258 Hom.: 175 Cov.: 32 AF XY: 0.0241 AC XY: 1790 AN XY: 74428

Gnomad4 AFR AF: 0.0853

Gnomad4 AMR AF: 0.00915

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.00439 Hom.: 37

Bravo AF: 0.0282

ESP6500AA AF: 0.0835 AC: 368

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00764 AC: 928

Asia WGS AF: 0.00318 AC: 12 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

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	Jun 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.014	N
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.20	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Benign	0.090
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.041	D
Polyphen		1.0	D
Vest4		0.070
MVP		0.43
MPC		0.36
ClinPred		0.075	T
GERP RS		2.6
Varity_R		0.32
gMVP		0.16

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: rs61751929; hg19: chr1-247768948;