2-240029751-G-A

Variant names:

• chr2-240029751-G-A
• rs60841887
• NM_001005853.1:c.679C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001005853.1(OR6B2):​c.679C>T​(p.Arg227Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 1,610,234 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R227S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.012 (35 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (31 hom.)
• Consequence: OR6B2 NM_001005853.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753
• Publications: 4 publications found

Genes affected

OR6B2 (HGNC:15041): (olfactory receptor family 6 subfamily B 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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034832954).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0121 (1849/152264) while in subpopulation AFR AF = 0.0423 (1757/41542). AF 95% confidence interval is 0.0406. There are 35 homozygotes in GnomAd4. There are 870 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR6B2	NM_001005853.1	c.679C>T	p.Arg227Cys	missense_variant	Exon 1 of 1	ENST00000319423.5	NP_001005853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR6B2	ENST00000319423.5	c.679C>T	p.Arg227Cys	missense_variant	Exon 1 of 1	6	NM_001005853.1	ENSP00000322435.5

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1849 AN: 152146 Hom.: 34 Cov.: 32

Gnomad AFR AF: 0.0424

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00296 AC: 738 AN: 249500 AF XY: 0.00216

Gnomad AFR exome AF: 0.0401

Gnomad AMR exome AF: 0.00246

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00165

GnomAD4 exome AF: 0.00126 AC: 1840 AN: 1457970 Hom.: 31 Cov.: 29 AF XY: 0.00108 AC XY: 780 AN XY: 725492

African (AFR) AF: 0.0427 AC: 1426 AN: 33424

American (AMR) AF: 0.00255 AC: 114 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000278 AC: 24 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00486 AC: 28 AN: 5760

European-Non Finnish (NFE) AF: 0.0000902 AC: 100 AN: 1108440

Other (OTH) AF: 0.00246 AC: 148 AN: 60234

GnomAD4 genome AF: 0.0121 AC: 1849 AN: 152264 Hom.: 35 Cov.: 32 AF XY: 0.0117 AC XY: 870 AN XY: 74446

African (AFR) AF: 0.0423 AC: 1757 AN: 41542

American (AMR) AF: 0.00418 AC: 64 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68020

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00452 Hom.: 24

Bravo AF: 0.0140

ESP6500AA AF: 0.0403 AC: 171

ESP6500EA AF: 0.000118 AC: 1

ExAC AF: 0.00367 AC: 445

Asia WGS AF: 0.00491 AC: 18 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.6
DANN	Benign	0.83
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-0.75
PrimateAI	Benign	0.18	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.048
Sift	Benign	0.070	T
Sift4G	Uncertain	0.027	D
Polyphen		0.051	B
Vest4		0.085
MVP		0.41
MPC		0.92
ClinPred		0.011	T
GERP RS		0.51
Varity_R		0.16
gMVP		0.27
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs60841887; hg19: chr2-240969168; COSMIC: COSV99048238; COSMIC: COSV99048238;