1-248626738-C-T

Variant names:

• chr1-248626738-C-T
• rs765476981
• NM_001001964.2:c.391G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001001964.2(OR2T11):​c.391G>A​(p.Val131Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V131F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: OR2T11 NM_001001964.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.09
• Publications: 2 publications found

Genes affected

OR2T11 (HGNC:19574): (olfactory receptor family 2 subfamily T member 11) 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

ENSG00000229255 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13485265).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001964.2. 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
	OR2T11	NM_001001964.2	MANE Select	c.391G>A	p.Val131Ile	missense	Exon 2 of 2	NP_001001964.1	Q8NH01

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T11	ENST00000641193.1	MANE Select	c.391G>A	p.Val131Ile	missense	Exon 2 of 2	ENSP00000492951.1	Q8NH01
	ENSG00000229255	ENST00000450847.2	TSL:2	n.195+15928G>A		intron	N/A
	ENSG00000229255	ENST00000825060.1		n.242+15928G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1430508 Hom.: 0 Cov.: 38 AF XY: 0.00000140 AC XY: 1 AN XY: 711852

African (AFR) AF: 0.00 AC: 0 AN: 30724

American (AMR) AF: 0.00 AC: 0 AN: 43682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25740

East Asian (EAS) AF: 0.00 AC: 0 AN: 38720

South Asian (SAS) AF: 0.00 AC: 0 AN: 84382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 9.17e-7 AC: 1 AN: 1090862

Other (OTH) AF: 0.00 AC: 0 AN: 59200

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.9
DANN	Benign	0.60
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.00062	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.95	L
PhyloP100		-3.1
PrimateAI	Benign	0.37	T
Polyphen		0.023	B
MutPred		0.34		Loss of catalytic residue at V131 (P = 0.0109)
ClinPred		0.093	T
GERP RS		3.5
Varity_R		0.051
gMVP		0.061
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: rs765476981; hg19: chr1-248790039;