NM_001004492.2:c.668G>A

Variant names:

• chr1-247451315-C-T
• rs4925663
• NM_001004492.2:c.668G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004492.2(OR2B11):​c.668G>A​(p.Gly223Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 1,613,724 control chromosomes in the GnomAD database, including 128,635 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (10382 hom., cov: 31)
  • Exomes 𝑓: 0.40 (118253 hom.)
• Consequence: OR2B11 NM_001004492.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353
• Publications: 36 publications found

Genes affected

OR2B11 (HGNC:31249): (olfactory receptor family 2 subfamily B member 11) 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=6.0917282E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004492.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2B11	NM_001004492.2	MANE Select	c.668G>A	p.Gly223Asp	missense	Exon 2 of 2	NP_001004492.1
	OR2B11	NR_169840.1		n.1322G>A		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2B11	ENST00000641149.2	MANE Select	c.668G>A	p.Gly223Asp	missense	Exon 2 of 2	ENSP00000492892.1
	OR2B11	ENST00000641527.1		c.668G>A	p.Gly223Asp	missense	Exon 3 of 3	ENSP00000493421.1
	OR2B11	ENST00000641613.1		n.1322G>A		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54251 AN: 151796 Hom.: 10365 Cov.: 31

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.344

GnomAD2 exomes AF: 0.406 AC: 101977 AN: 251356 AF XY: 0.406

Gnomad AFR exome AF: 0.230

Gnomad AMR exome AF: 0.480

Gnomad ASJ exome AF: 0.225

Gnomad EAS exome AF: 0.519

Gnomad FIN exome AF: 0.432

Gnomad NFE exome AF: 0.391

Gnomad OTH exome AF: 0.392

GnomAD4 exome AF: 0.398 AC: 582193 AN: 1461810 Hom.: 118253 Cov.: 61 AF XY: 0.400 AC XY: 290703 AN XY: 727218

African (AFR) AF: 0.223 AC: 7452 AN: 33480

American (AMR) AF: 0.477 AC: 21341 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 5838 AN: 26136

East Asian (EAS) AF: 0.490 AC: 19437 AN: 39698

South Asian (SAS) AF: 0.445 AC: 38342 AN: 86254

European-Finnish (FIN) AF: 0.436 AC: 23317 AN: 53420

Middle Eastern (MID) AF: 0.220 AC: 1269 AN: 5768

European-Non Finnish (NFE) AF: 0.398 AC: 442620 AN: 1111938

Other (OTH) AF: 0.374 AC: 22577 AN: 60392

GnomAD4 genome AF: 0.357 AC: 54285 AN: 151914 Hom.: 10382 Cov.: 31 AF XY: 0.362 AC XY: 26900 AN XY: 74228

African (AFR) AF: 0.232 AC: 9611 AN: 41448

American (AMR) AF: 0.433 AC: 6612 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 758 AN: 3472

East Asian (EAS) AF: 0.509 AC: 2624 AN: 5152

South Asian (SAS) AF: 0.464 AC: 2230 AN: 4808

European-Finnish (FIN) AF: 0.444 AC: 4679 AN: 10530

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26732 AN: 67920

Other (OTH) AF: 0.349 AC: 735 AN: 2108

Alfa AF: 0.382 Hom.: 38892

Bravo AF: 0.349

TwinsUK AF: 0.400 AC: 1482

ALSPAC AF: 0.411 AC: 1583

ESP6500AA AF: 0.236 AC: 1040

ESP6500EA AF: 0.390 AC: 3350

ExAC AF: 0.401 AC: 48726

Asia WGS AF: 0.478 AC: 1663 AN: 3478

EpiCase AF: 0.370

EpiControl AF: 0.371

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.000061	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		0.35
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.055	T
Polyphen		0.35	B
Vest4		0.18
MPC		0.30
ClinPred		0.068	T
GERP RS		4.2
Varity_R		0.82
gMVP		0.58
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs4925663; hg19: chr1-247614617; COSMIC: COSV59509275; COSMIC: COSV59509275;