chr1-248638649-C-G

Variant names:

• chr1-248638649-C-G
• rs112397726
• NM_001001827.2:c.610G>C

Variant summary

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

The NM_001001827.2(OR2T35):​c.610G>C​(p.Val204Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V204M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00056 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0048 (9 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T35 NM_001001827.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309
• Publications: 3 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=0.0016014576).

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.610G>C	p.Val204Leu	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.610G>C	p.Val204Leu	missense	Exon 2 of 2	ENSP00000492995.1	Q8NGX2
	ENSG00000229255	ENST00000450847.2	TSL:2	n.195+4017G>C		intron	N/A
	ENSG00000229255	ENST00000825060.1		n.242+4017G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000560 AC: 3 AN: 5356 Hom.: 1 Cov.: 0

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: 0.0109

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000161 AC: 24 AN: 149236 AF XY: 0.0000746

Gnomad AFR exome AF: 0.000423

Gnomad AMR exome AF: 0.0000529

Gnomad ASJ exome AF: 0.000290

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000147

Gnomad NFE exome AF: 0.000205

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00480 AC: 76 AN: 15838 Hom.: 9 Cov.: 0 AF XY: 0.00598 AC XY: 46 AN XY: 7686

African (AFR) AF: 0.00 AC: 0 AN: 6018

American (AMR) AF: 0.00 AC: 0 AN: 476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 292

East Asian (EAS) AF: 0.00 AC: 0 AN: 446

South Asian (SAS) AF: 0.00 AC: 0 AN: 1168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 56

European-Non Finnish (NFE) AF: 0.0121 AC: 72 AN: 5956

Other (OTH) AF: 0.00508 AC: 4 AN: 788

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000560 AC: 3 AN: 5356 Hom.: 1 Cov.: 0 AF XY: 0.00121 AC XY: 3 AN XY: 2472

African (AFR) AF: 0.00 AC: 0 AN: 4804

American (AMR) AF: 0.00 AC: 0 AN: 118

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 36

East Asian (EAS) AF: 0.00 AC: 0 AN: 16

South Asian (SAS) AF: 0.00 AC: 0 AN: 20

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0109 AC: 3 AN: 276

Other (OTH) AF: 0.00 AC: 0 AN: 46

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00517 AC: 65

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.31
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.074
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.046	D
Polyphen		0.92	P
Vest4		0.13
MutPred		0.33		Loss of sheet (P = 0.437)
MVP		0.40
MPC		2.2
ClinPred		0.10	T
GERP RS		1.9
Varity_R		0.50
gMVP		0.075
Mutation Taster		=97/3	polymorphism (auto)

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: rs112397726; hg19: chr1-248801950; COSMIC: COSV58085455; COSMIC: COSV58085455;