1-248638520-C-A

Variant names:

• chr1-248638520-C-A
• rs1236670402
• NM_001001827.2:c.739G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001001827.2(OR2T35):​c.739G>T​(p.Val247Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000015 (0 hom., cov: 19)
  • Exomes 𝑓: 0.0000076 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T35 NM_001001827.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03
• 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.38038057).

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.739G>T	p.Val247Leu	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.739G>T	p.Val247Leu	missense	Exon 2 of 2	ENSP00000492995.1	Q8NGX2
	ENSG00000229255	ENST00000450847.2	TSL:2	n.195+4146G>T		intron	N/A
	ENSG00000229255	ENST00000825060.1		n.242+4146G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000151 AC: 2 AN: 132052 Hom.: 0 Cov.: 19

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: 0.0000322

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000198 AC: 3 AN: 151816 AF XY: 0.0000372

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: 0.0000520

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000763 AC: 10 AN: 1310950 Hom.: 0 Cov.: 25 AF XY: 0.00000913 AC XY: 6 AN XY: 657306

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

African (AFR) AF: 0.00 AC: 0 AN: 28496

American (AMR) AF: 0.00 AC: 0 AN: 42606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25028

East Asian (EAS) AF: 0.00 AC: 0 AN: 38608

South Asian (SAS) AF: 0.00 AC: 0 AN: 82632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5514

European-Non Finnish (NFE) AF: 0.0000102 AC: 10 AN: 981048

Other (OTH) AF: 0.00 AC: 0 AN: 55424

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000533294), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000151 AC: 2 AN: 132172 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 64086

African (AFR) AF: 0.00 AC: 0 AN: 32842

American (AMR) AF: 0.00 AC: 0 AN: 13666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3152

East Asian (EAS) AF: 0.00 AC: 0 AN: 4528

South Asian (SAS) AF: 0.00 AC: 0 AN: 4100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.0000322 AC: 2 AN: 62082

Other (OTH) AF: 0.00 AC: 0 AN: 1816

Alfa AF: 0.00 Hom.: 0

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	Pathogenic	0.58
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	-0.011
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.00064	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		1.0
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.088
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.64		Loss of sheet (P = 0.1158)
MVP		0.48
MPC		2.9
ClinPred		0.76	D
GERP RS		2.9
Varity_R		0.76
gMVP		0.071
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs1236670402; hg19: chr1-248801821;