1-248638867-C-T

Variant names:

• chr1-248638867-C-T
• rs549888308
• NM_001001827.2:c.392G>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.392G>A​(p.Arg131Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 5)
  • Exomes 𝑓: 0.000093 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T35 NM_001001827.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.21
• Publications: 0 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=0.04664901).

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.392G>A	p.Arg131Gln	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.392G>A	p.Arg131Gln	missense	Exon 2 of 2	ENSP00000492995.1	Q8NGX2
	ENSG00000229255	ENST00000450847.2	TSL:2	n.195+3799G>A		intron	N/A
	ENSG00000229255	ENST00000825060.1		n.242+3799G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 30372 Hom.: 0 Cov.: 5

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000245 AC: 18 AN: 73528 AF XY: 0.000186

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.0000675

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000583

Gnomad OTH exome AF: 0.000942

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000926 AC: 58 AN: 626608 Hom.: 0 Cov.: 8 AF XY: 0.0000908 AC XY: 30 AN XY: 330530

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

African (AFR) AF: 0.000102 AC: 2 AN: 19530

American (AMR) AF: 0.0000299 AC: 1 AN: 33444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17328

East Asian (EAS) AF: 0.00 AC: 0 AN: 33920

South Asian (SAS) AF: 0.00 AC: 0 AN: 62202

European-Finnish (FIN) AF: 0.0000258 AC: 1 AN: 38770

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2694

European-Non Finnish (NFE) AF: 0.000130 AC: 50 AN: 386084

Other (OTH) AF: 0.000123 AC: 4 AN: 32636

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 30372 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 14384

African (AFR) AF: 0.00 AC: 0 AN: 9312

American (AMR) AF: 0.00 AC: 0 AN: 3204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 736

East Asian (EAS) AF: 0.00 AC: 0 AN: 1378

South Asian (SAS) AF: 0.00 AC: 0 AN: 742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 84

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 12616

Other (OTH) AF: 0.00 AC: 0 AN: 344

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000267 AC: 21

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	0.11
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.00085	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.4	L
PhyloP100		-1.2
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.081
Sift	Benign	0.075	T
Sift4G	Benign	0.14	T
Polyphen		0.80	P
Vest4		0.18
MVP		0.47
MPC		2.2
ClinPred		0.037	T
GERP RS		1.8
Varity_R		0.12
gMVP		0.078
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs549888308; hg19: chr1-248802168;