1-248650085-G-C

Variant names:

• chr1-248650085-G-C
• rs756636325
• NM_001001824.2:c.800C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001001824.2(OR2T27):​c.800C>G​(p.Thr267Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000313 in 1,573,184 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (4 hom., cov: 26)
  • Exomes 𝑓: 0.00031 (27 hom.)
• Consequence: OR2T27 NM_001001824.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.383
• Publications: 1 publications found

Genes affected

OR2T27 (HGNC:31252): (olfactory receptor family 2 subfamily T member 27) 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.

• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001824.2. 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
	OR2T27	NM_001001824.2	MANE Select	c.800C>G	p.Thr267Ser	missense	Exon 2 of 2	NP_001001824.1	Q8NH04
	OR2T27	NM_001386060.1		c.800C>G	p.Thr267Ser	missense	Exon 3 of 3	NP_001372989.1	Q8NH04

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T27	ENST00000460972.4	TSL:6 MANE Select	c.800C>G	p.Thr267Ser	missense	Exon 2 of 2	ENSP00000493412.1	Q8NH04
	OR2T27	ENST00000641652.1		c.800C>G	p.Thr267Ser	missense	Exon 3 of 3	ENSP00000493434.1	Q8NH04

Frequencies

GnomAD3 genomes AF: 0.000353 AC: 51 AN: 144460 Hom.: 4 Cov.: 26

Gnomad AFR AF: 0.0000260

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000478

Gnomad ASJ AF: 0.00850

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000182

Gnomad OTH AF: 0.000998

GnomAD2 exomes AF: 0.000294 AC: 72 AN: 245084 AF XY: 0.000249

Gnomad AFR exome AF: 0.0000645

Gnomad AMR exome AF: 0.000178

Gnomad ASJ exome AF: 0.00393

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000189

Gnomad OTH exome AF: 0.000832

GnomAD4 exome AF: 0.000309 AC: 442 AN: 1428724 Hom.: 27 Cov.: 33 AF XY: 0.000277 AC XY: 197 AN XY: 711310

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

African (AFR) AF: 0.0000311 AC: 1 AN: 32178

American (AMR) AF: 0.000434 AC: 19 AN: 43816

Ashkenazi Jewish (ASJ) AF: 0.00685 AC: 177 AN: 25852

East Asian (EAS) AF: 0.0000259 AC: 1 AN: 38568

South Asian (SAS) AF: 0.0000356 AC: 3 AN: 84242

European-Finnish (FIN) AF: 0.0000388 AC: 2 AN: 51548

Middle Eastern (MID) AF: 0.00105 AC: 6 AN: 5694

European-Non Finnish (NFE) AF: 0.000175 AC: 190 AN: 1087596

Other (OTH) AF: 0.000726 AC: 43 AN: 59230

⚠️ 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: 0.000353 AC: 51 AN: 144460 Hom.: 4 Cov.: 26 AF XY: 0.000470 AC XY: 33 AN XY: 70180

African (AFR) AF: 0.0000260 AC: 1 AN: 38512

American (AMR) AF: 0.000478 AC: 7 AN: 14638

Ashkenazi Jewish (ASJ) AF: 0.00850 AC: 29 AN: 3410

East Asian (EAS) AF: 0.00 AC: 0 AN: 4854

South Asian (SAS) AF: 0.00 AC: 0 AN: 4442

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000182 AC: 12 AN: 65828

Other (OTH) AF: 0.000998 AC: 2 AN: 2004

Alfa AF: 0.00120 Hom.: 3

ExAC AF: 0.000450 AC: 54

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	0.094
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	20
DANN	Benign	0.29
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.0091	T
MetaSVM	Benign	-0.94	T
PhyloP100		0.38
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.098
Sift	Benign	0.49	T
Sift4G	Benign	1.0	T
Polyphen		0.43	B
Vest4		0.092
MutPred		0.39		Gain of disorder (P = 0.0363)
MVP		0.27
MPC		0.53
ClinPred		0.069	T
GERP RS		2.5
Varity_R		0.10
gMVP		0.051
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.31		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs756636325; hg19: chr1-248813386;