NM_001005853.1:c.803A>T

Variant names:

• chr2-240029627-T-A
• rs61730693
• NM_001005853.1:c.803A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001005853.1(OR6B2):​c.803A>T​(p.Gln268Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00344 in 1,501,360 control chromosomes in the GnomAD database, including 169 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (82 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (87 hom.)
• Consequence: OR6B2 NM_001005853.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.06
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026026368).
• BP6: Variant 2-240029627-T-A is Benign according to our data. Variant chr2-240029627-T-A is described in ClinVar as Benign. ClinVar VariationId is 784463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.

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.803A>T	p.Gln268Leu	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.803A>T	p.Gln268Leu	missense	Exon 1 of 1	ENSP00000322435.5	Q6IFH4

Frequencies

GnomAD3 genomes AF: 0.0176 AC: 2682 AN: 152120 Hom.: 81 Cov.: 32

Gnomad AFR AF: 0.0613

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00469 AC: 1170 AN: 249528 AF XY: 0.00367

Gnomad AFR exome AF: 0.0641

Gnomad AMR exome AF: 0.00408

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: 0.00297

GnomAD4 exome AF: 0.00183 AC: 2473 AN: 1349122 Hom.: 87 Cov.: 21 AF XY: 0.00164 AC XY: 1112 AN XY: 677688

African (AFR) AF: 0.0602 AC: 1880 AN: 31218

American (AMR) AF: 0.00428 AC: 191 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25410

East Asian (EAS) AF: 0.00 AC: 0 AN: 39188

South Asian (SAS) AF: 0.000238 AC: 20 AN: 83910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00398 AC: 22 AN: 5532

European-Non Finnish (NFE) AF: 0.000125 AC: 126 AN: 1009272

Other (OTH) AF: 0.00413 AC: 234 AN: 56616

GnomAD4 genome AF: 0.0176 AC: 2687 AN: 152238 Hom.: 82 Cov.: 32 AF XY: 0.0171 AC XY: 1271 AN XY: 74450

African (AFR) AF: 0.0613 AC: 2544 AN: 41518

American (AMR) AF: 0.00693 AC: 106 AN: 15296

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68016

Other (OTH) AF: 0.00994 AC: 21 AN: 2112

Alfa AF: 0.00104 Hom.: 3

Bravo AF: 0.0200

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0560 AC: 222

ESP6500EA AF: 0.000362 AC: 3

ExAC AF: 0.00544 AC: 658

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.68
DANN	Benign	0.83
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.029	T
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.065	N
PhyloP100		-1.1
PrimateAI	Benign	0.19	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.018
Sift	Benign	0.26	T
Sift4G	Benign	0.75	T
Polyphen		0.0	B
Vest4		0.053
MVP		0.13
MPC		0.66
ClinPred		0.0029	T
GERP RS		1.3
Varity_R		0.062
gMVP		0.20
Mutation Taster		=97/3	polymorphism (auto)

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: rs61730693; hg19: chr2-240969044;