rs954475

Positions:

• chr1-248388335-T-G

Variant summary

Our verdict is Benign. Variant got -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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
OR2T6	NM_001005471.2	c.727T>G	p.Ser243Ala	missense_variant	3/3	ENST00000641644.1	NP_001005471.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2T6	ENST00000641644.1	c.727T>G	p.Ser243Ala	missense_variant	3/3		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

GnomAD3 exomes AF: 0.242 AC: 60725 AN: 250636 Hom.: 8976 AF XY: 0.236 AC XY: 31972 AN XY: 135424

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 SAS exome AF: 0.333

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

Gnomad4 AFR exome AF: 0.454

Gnomad4 AMR exome AF: 0.325

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.415

Gnomad4 SAS exome AF: 0.329

Gnomad4 FIN exome AF: 0.199

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.202

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

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.228

Alfa AF: 0.193 Hom.: 3414

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
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs954475; hg19: chr1-248551636; COSMIC: COSV63216307;