chr2-240029913-C-T

Variant names:

• chr2-240029913-C-T
• rs770553143
• NM_001005853.1:c.517G>A

Variant summary

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

The NM_001005853.1(OR6B2):​c.517G>A​(p.Val173Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000338 in 1,447,570 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 0.000059 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: OR6B2 NM_001005853.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.13
• Publications: 3 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=0.010374337).

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.517G>A	p.Val173Ile	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.517G>A	p.Val173Ile	missense	Exon 1 of 1	ENSP00000322435.5	Q6IFH4

Frequencies

GnomAD3 genomes AF: 0.0000593 AC: 9 AN: 151680 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000962 AC: 23 AN: 239038 AF XY: 0.000108

Gnomad AFR exome AF: 0.000142

Gnomad AMR exome AF: 0.0000300

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000812

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000557

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000309 AC: 40 AN: 1295772 Hom.: 0 Cov.: 19 AF XY: 0.0000383 AC XY: 25 AN XY: 653512

African (AFR) AF: 0.0000663 AC: 2 AN: 30152

American (AMR) AF: 0.0000227 AC: 1 AN: 43966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25068

East Asian (EAS) AF: 0.000412 AC: 16 AN: 38836

South Asian (SAS) AF: 0.0000242 AC: 2 AN: 82768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5476

European-Non Finnish (NFE) AF: 0.0000187 AC: 18 AN: 961502

Other (OTH) AF: 0.0000182 AC: 1 AN: 54876

GnomAD4 genome AF: 0.0000593 AC: 9 AN: 151798 Hom.: 0 Cov.: 29 AF XY: 0.0000539 AC XY: 4 AN XY: 74174

African (AFR) AF: 0.00 AC: 0 AN: 41334

American (AMR) AF: 0.00 AC: 0 AN: 15256

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

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10540

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

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000745 AC: 9

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	0.083
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.28
DANN	Benign	0.79
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0082	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.00089	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.84	L
PhyloP100		-1.1
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.016
Sift	Benign	0.49	T
Sift4G	Benign	0.53	T
Polyphen		0.0020	B
Vest4		0.024
MutPred		0.43		Loss of sheet (P = 0.1907)
MVP		0.13
MPC		0.57
ClinPred		0.011	T
GERP RS		0.38
Varity_R		0.035
gMVP		0.085
Mutation Taster		=98/2	polymorphism

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: rs770553143; hg19: chr2-240969330; COSMIC: COSV53157676; COSMIC: COSV53157676;