1-248638558-C-T

Variant names:

• chr1-248638558-C-T
• rs766235740
• NM_001001827.2:c.701G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001001827.2(OR2T35):​c.701G>A​(p.Arg234Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 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. R234W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000029 (0 hom., cov: 19)
  • Exomes 𝑓: 0.000011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T35 NM_001001827.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957
• Publications: 1 publications found

Genes affected

OR2T35 (HGNC:31257): (olfactory receptor family 2 subfamily T member 35) 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]

ENSG00000229255 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05790311).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001827.2. 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
	OR2T35	NM_001001827.2	MANE Select	c.701G>A	p.Arg234Gln	missense	Exon 2 of 2	NP_001001827.1	Q8NGX2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T35	ENST00000641268.1	MANE Select	c.701G>A	p.Arg234Gln	missense	Exon 2 of 2	ENSP00000492995.1	Q8NGX2
	ENSG00000229255	ENST00000450847.2	TSL:2	n.195+4108G>A		intron	N/A
	ENSG00000229255	ENST00000825060.1		n.242+4108G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000295 AC: 4 AN: 135760 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.0000900

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000709

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000209 AC: 5 AN: 239412 AF XY: 0.0000154

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000894

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000924

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000105 AC: 15 AN: 1426974 Hom.: 0 Cov.: 32 AF XY: 0.0000113 AC XY: 8 AN XY: 710786

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

African (AFR) AF: 0.0000326 AC: 1 AN: 30708

American (AMR) AF: 0.0000911 AC: 4 AN: 43894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25778

East Asian (EAS) AF: 0.00 AC: 0 AN: 39286

South Asian (SAS) AF: 0.0000235 AC: 2 AN: 85102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.00000645 AC: 7 AN: 1085182

Other (OTH) AF: 0.0000169 AC: 1 AN: 59162

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000367574), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000295 AC: 4 AN: 135760 Hom.: 0 Cov.: 19 AF XY: 0.0000152 AC XY: 1 AN XY: 65902

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

African (AFR) AF: 0.0000900 AC: 3 AN: 33338

American (AMR) AF: 0.0000709 AC: 1 AN: 14102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3240

East Asian (EAS) AF: 0.00 AC: 0 AN: 4706

South Asian (SAS) AF: 0.00 AC: 0 AN: 4312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 63808

Other (OTH) AF: 0.00 AC: 0 AN: 1896

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000252 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.96
PrimateAI	Benign	0.18	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.055
Sift	Benign	0.065	T
Sift4G	Benign	0.11	T
Polyphen		0.13	B
Vest4		0.16
MutPred		0.52		Loss of methylation at R234 (P = 0.0194)
MVP		0.45
MPC		1.9
ClinPred		0.59	D
GERP RS		0.93
Varity_R		0.11
gMVP		0.13
Mutation Taster		=96/4	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: rs766235740; hg19: chr1-248801859; COSMIC: COSV100442293; COSMIC: COSV100442293;