chr1-248361696-C-T

Variant names:

• chr1-248361696-C-T
• rs774089576
• NM_001004696.2:c.32C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001004696.2(OR2T4):​c.32C>T​(p.Thr11Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,251,624 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000034 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000018 (1 hom.)
• Consequence: OR2T4 NM_001004696.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33
• Publications: 1 publications found

Genes affected

OR2T4 (HGNC:15016): (olfactory receptor family 2 subfamily T member 4) 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28891772).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004696.2. 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
	OR2T4	NM_001004696.2	MANE Select	c.32C>T	p.Thr11Ile	missense	Exon 1 of 1	NP_001004696.2	A0A2C9F2M9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T4	ENST00000366473.4	TSL:6 MANE Select	c.32C>T	p.Thr11Ile	missense	Exon 1 of 1	ENSP00000355429.3	A0A2C9F2M9

Frequencies

GnomAD3 genomes AF: 0.0000343 AC: 4 AN: 116472 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000797

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000176 AC: 20 AN: 1135152 Hom.: 1 Cov.: 31 AF XY: 0.0000108 AC XY: 6 AN XY: 557820

African (AFR) AF: 0.00 AC: 0 AN: 32250

American (AMR) AF: 0.00 AC: 0 AN: 29156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21460

East Asian (EAS) AF: 0.00 AC: 0 AN: 15898

South Asian (SAS) AF: 0.00 AC: 0 AN: 49806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4492

European-Non Finnish (NFE) AF: 0.0000211 AC: 19 AN: 900016

Other (OTH) AF: 0.0000217 AC: 1 AN: 46150

GnomAD4 genome AF: 0.0000343 AC: 4 AN: 116472 Hom.: 0 Cov.: 30 AF XY: 0.0000178 AC XY: 1 AN XY: 56204

African (AFR) AF: 0.00 AC: 0 AN: 39246

American (AMR) AF: 0.00 AC: 0 AN: 9856

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2730

East Asian (EAS) AF: 0.00 AC: 0 AN: 1986

South Asian (SAS) AF: 0.00 AC: 0 AN: 2528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.0000797 AC: 4 AN: 50218

Other (OTH) AF: 0.00 AC: 0 AN: 1604

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000227

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	0.32
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.3
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.096
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.84	P
Vest4		0.17
MutPred		0.51		Loss of solvent accessibility (P = 0.3103)
MVP		0.72
MPC		0.44
ClinPred		0.99	D
GERP RS		1.6
PromoterAI		0.017	Neutral
Varity_R		0.20
gMVP		0.29
Mutation Taster		=90/10	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: rs774089576; hg19: chr1-248524998;