1-248650078-C-G

Variant names:

• chr1-248650078-C-G
• rs751281848
• NM_001001824.2:c.807G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001001824.2(OR2T27):​c.807G>C​(p.Glu269Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,429,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E269A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: OR2T27 NM_001001824.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 3 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050079167).

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.807G>C	p.Glu269Asp	missense	Exon 2 of 2	NP_001001824.1	Q8NH04
	OR2T27	NM_001386060.1		c.807G>C	p.Glu269Asp	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.807G>C	p.Glu269Asp	missense	Exon 2 of 2	ENSP00000493412.1	Q8NH04
	OR2T27	ENST00000641652.1		c.807G>C	p.Glu269Asp	missense	Exon 3 of 3	ENSP00000493434.1	Q8NH04

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD2 exomes AF: 0.00000407 AC: 1 AN: 245428 AF XY: 0.00000753

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000898

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1429118 Hom.: 0 Cov.: 33 AF XY: 0.00000141 AC XY: 1 AN XY: 711472

African (AFR) AF: 0.00 AC: 0 AN: 32042

American (AMR) AF: 0.00 AC: 0 AN: 43826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25874

East Asian (EAS) AF: 0.00 AC: 0 AN: 38564

South Asian (SAS) AF: 0.00 AC: 0 AN: 84264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1088060

Other (OTH) AF: 0.00 AC: 0 AN: 59238

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.89
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.1	T
PhyloP100		-1.7
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.013
Sift	Benign	0.14	T
Sift4G	Benign	0.40	T
Polyphen		0.044	B
Vest4		0.070
MutPred		0.29		Loss of ubiquitination at K272 (P = 0.1055)
MVP		0.28
MPC		0.45
ClinPred		0.063	T
GERP RS		0.29
Varity_R		0.11
gMVP		0.067
Mutation Taster		=100/0	polymorphism

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: rs751281848; hg19: chr1-248813379;