NM_001005853.1:c.645A>G

Variant names:

• chr2-240029785-T-C
• rs369167490
• NM_001005853.1:c.645A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005853.1(OR6B2):​c.645A>G​(p.Ile215Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000221 in 1,609,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: OR6B2 NM_001005853.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.66
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.042414993).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005853.1. 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
	OR6B2	NM_001005853.1	MANE Select	c.645A>G	p.Ile215Met	missense	Exon 1 of 1	NP_001005853.1	Q6IFH4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR6B2	ENST00000319423.5	TSL:6 MANE Select	c.645A>G	p.Ile215Met	missense	Exon 1 of 1	ENSP00000322435.5	Q6IFH4

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152054 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000842 AC: 21 AN: 249418 AF XY: 0.0000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000228 AC: 332 AN: 1456846 Hom.: 0 Cov.: 29 AF XY: 0.000239 AC XY: 173 AN XY: 725066

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000299 AC: 1 AN: 33400

American (AMR) AF: 0.000179 AC: 8 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000280 AC: 310 AN: 1107380

Other (OTH) AF: 0.000199 AC: 12 AN: 60240

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152172 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74396

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000482 AC: 2 AN: 41500

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2112

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000192365), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000171 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000118 AC: 1

ExAC AF: 0.000297 AC: 36

EpiCase AF: 0.000436

EpiControl AF: 0.0000594

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.35
DANN	Benign	0.56
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.036	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.3	L
PhyloP100		-3.7
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.030
Sift	Benign	0.12	T
Sift4G	Benign	0.16	T
Polyphen		0.0010	B
Vest4		0.057
MVP		0.17
MPC		0.69
ClinPred		0.047	T
GERP RS		-5.9
Varity_R		0.11
gMVP		0.23
Mutation Taster		=97/3	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: rs369167490; hg19: chr2-240969202;