1-248488771-C-A

Variant names:

• chr1-248488771-C-A
• rs1161068370
• NM_001004697.2:c.183C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004697.2(OR2T5):​c.183C>A​(p.Ser61Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000095 (0 hom., cov: 14)
  • Exomes 𝑓: 0.000020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T5 NM_001004697.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68
• Publications: 1 publications found

Genes affected

OR2T5 (HGNC:15017): (olfactory receptor family 2 subfamily T member 5) 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15872017).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004697.2. 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
	OR2T5	NM_001004697.2	MANE Select	c.183C>A	p.Ser61Arg	missense	Exon 1 of 1	NP_001004697.1	Q6IEZ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T5	ENST00000641363.1	MANE Select	c.183C>A	p.Ser61Arg	missense	Exon 1 of 1	ENSP00000493066.1	Q6IEZ7
	ENSG00000229255	ENST00000450847.2	TSL:2	n.279-3287G>T		intron	N/A
	ENSG00000229255	ENST00000825060.1		n.326-3287G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000951 AC: 11 AN: 115724 Hom.: 0 Cov.: 14

Gnomad AFR AF: 0.000531

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: 0.0000257 AC: 6 AN: 233368 AF XY: 0.0000236

Gnomad AFR exome AF: 0.000594

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000200 AC: 26 AN: 1299694 Hom.: 0 Cov.: 22 AF XY: 0.0000199 AC XY: 13 AN XY: 654486

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

African (AFR) AF: 0.000806 AC: 19 AN: 23586

American (AMR) AF: 0.00 AC: 0 AN: 44504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25074

East Asian (EAS) AF: 0.00 AC: 0 AN: 38376

South Asian (SAS) AF: 0.00 AC: 0 AN: 81286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.000188 AC: 1 AN: 5318

European-Non Finnish (NFE) AF: 0.00000411 AC: 4 AN: 973842

Other (OTH) AF: 0.0000368 AC: 2 AN: 54398

⚠️ 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: AS_VQSR AF: 0.0000950 AC: 11 AN: 115788 Hom.: 0 Cov.: 14 AF XY: 0.000108 AC XY: 6 AN XY: 55722

African (AFR) AF: 0.000529 AC: 11 AN: 20794

American (AMR) AF: 0.00 AC: 0 AN: 12524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3122

East Asian (EAS) AF: 0.00 AC: 0 AN: 4152

South Asian (SAS) AF: 0.00 AC: 0 AN: 3170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 60402

Other (OTH) AF: 0.00 AC: 0 AN: 1644

Alfa AF: 0.0000962 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.0
DANN	Benign	0.87
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0064	N
M_CAP	Benign	0.00054	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.5	L
PhyloP100		-2.7
PrimateAI	Benign	0.29	T
Polyphen		0.0	B
MutPred		0.74		Loss of catalytic residue at H60 (P = 0.1553)
ClinPred		0.029	T
GERP RS		-5.3
PromoterAI		-0.0078	Neutral
Varity_R		0.15
gMVP		0.098
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1161068370; hg19: chr1-248652072;