rs954475

Variant names:

• chr1-248388335-T-G
• rs954475
• NM_001005471.2:c.727T>G

Variant summary

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

The NM_001005471.2(OR2T6):​c.727T>G​(p.Ser243Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,613,124 control chromosomes in the GnomAD database, including 35,960 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (6486 hom., cov: 31)
  • Exomes 𝑓: 0.18 (29474 hom.)
• Consequence: OR2T6 NM_001005471.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248
• Publications: 24 publications found

Genes affected

OR2T6 (HGNC:15018): (olfactory receptor family 2 subfamily T member 6) 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=0.0025433302).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2T6	NM_001005471.2	c.727T>G	p.Ser243Ala	missense_variant	Exon 3 of 3	ENST00000641644.1	NP_001005471.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2T6	ENST00000641644.1	c.727T>G	p.Ser243Ala	missense_variant	Exon 3 of 3		NM_001005471.2	ENSP00000493366.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40011 AN: 151704 Hom.: 6453 Cov.: 31

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.227

GnomAD2 exomes AF: 0.242 AC: 60725 AN: 250636 AF XY: 0.236

Gnomad AFR exome AF: 0.441

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.440

Gnomad FIN exome AF: 0.201

Gnomad NFE exome AF: 0.151

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.184 AC: 268575 AN: 1461302 Hom.: 29474 Cov.: 35 AF XY: 0.187 AC XY: 135803 AN XY: 726944

African (AFR) AF: 0.454 AC: 15211 AN: 33472

American (AMR) AF: 0.325 AC: 14527 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 3237 AN: 26096

East Asian (EAS) AF: 0.415 AC: 16481 AN: 39682

South Asian (SAS) AF: 0.329 AC: 28337 AN: 86198

European-Finnish (FIN) AF: 0.199 AC: 10604 AN: 53390

Middle Eastern (MID) AF: 0.174 AC: 1002 AN: 5760

European-Non Finnish (NFE) AF: 0.150 AC: 166955 AN: 1111620

Other (OTH) AF: 0.202 AC: 12221 AN: 60374

GnomAD4 genome AF: 0.264 AC: 40091 AN: 151822 Hom.: 6486 Cov.: 31 AF XY: 0.269 AC XY: 19943 AN XY: 74210

African (AFR) AF: 0.438 AC: 18106 AN: 41350

American (AMR) AF: 0.288 AC: 4400 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3466

East Asian (EAS) AF: 0.430 AC: 2204 AN: 5120

South Asian (SAS) AF: 0.333 AC: 1595 AN: 4796

European-Finnish (FIN) AF: 0.197 AC: 2081 AN: 10578

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.157 AC: 10660 AN: 67924

Other (OTH) AF: 0.228 AC: 480 AN: 2108

Alfa AF: 0.200 Hom.: 4822

Bravo AF: 0.278

ESP6500AA AF: 0.436 AC: 1921

ESP6500EA AF: 0.151 AC: 1297

ExAC AF: 0.243 AC: 29449

Asia WGS AF: 0.386 AC: 1341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0093	T;T
Eigen	Benign	0.0046
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.15	N
MetaRNN	Benign	0.0025	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.4	M;M
PhyloP100		0.25
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.9	.;D
REVEL	Benign	0.096
Sift	Uncertain	0.0010	.;D
Sift4G	Uncertain	0.0080	.;D
Polyphen		1.0	D;D
Vest4		0.23
MPC		0.42
ClinPred		0.051	T
GERP RS		2.9
Varity_R		0.47
gMVP		0.040
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs954475; hg19: chr1-248551636; COSMIC: COSV63216307;