chr1-248650160-G-A

Variant names:

• chr1-248650160-G-A
• rs1322538046
• NM_001001824.2:c.725C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001001824.2(OR2T27):​c.725C>T​(p.Ser242Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000831 in 1,565,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000049 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: OR2T27 NM_001001824.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.642
• Publications: 1 publications found

Genes affected

OR2T27 (HGNC:31252): (olfactory receptor family 2 subfamily T member 27) 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21146104).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001824.2. 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
	OR2T27	NM_001001824.2	MANE Select	c.725C>T	p.Ser242Phe	missense	Exon 2 of 2	NP_001001824.1	Q8NH04
	OR2T27	NM_001386060.1		c.725C>T	p.Ser242Phe	missense	Exon 3 of 3	NP_001372989.1	Q8NH04

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T27	ENST00000460972.4	TSL:6 MANE Select	c.725C>T	p.Ser242Phe	missense	Exon 2 of 2	ENSP00000493412.1	Q8NH04
	OR2T27	ENST00000641652.1		c.725C>T	p.Ser242Phe	missense	Exon 3 of 3	ENSP00000493434.1	Q8NH04

Frequencies

GnomAD3 genomes AF: 0.0000491 AC: 7 AN: 142582 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000179

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: 0.0000167 AC: 4 AN: 239876 AF XY: 0.0000154

Gnomad AFR exome AF: 0.000260

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 AF: 0.00000422 AC: 6 AN: 1422616 Hom.: 0 Cov.: 33 AF XY: 0.00000706 AC XY: 5 AN XY: 708184

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

African (AFR) AF: 0.000184 AC: 6 AN: 32656

American (AMR) AF: 0.00 AC: 0 AN: 43202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25806

East Asian (EAS) AF: 0.00 AC: 0 AN: 38426

South Asian (SAS) AF: 0.00 AC: 0 AN: 83742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1082822

Other (OTH) AF: 0.00 AC: 0 AN: 59042

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000118267), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000491 AC: 7 AN: 142582 Hom.: 0 Cov.: 26 AF XY: 0.0000723 AC XY: 5 AN XY: 69152

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

African (AFR) AF: 0.000179 AC: 7 AN: 39060

American (AMR) AF: 0.00 AC: 0 AN: 14276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3370

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64542

Other (OTH) AF: 0.00 AC: 0 AN: 1968

⚠️ 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: 0.00000838 AC: 1

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	0.16
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Benign	0.081
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.78	T
PhyloP100		-0.64
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.16
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.038	D
Polyphen		0.73	P
Vest4		0.24
MutPred		0.53		Loss of disorder (P = 0.0167)
MVP		0.56
MPC		0.75
ClinPred		0.32	T
GERP RS		2.4
Varity_R		0.44
gMVP		0.12
Mutation Taster		=100/0	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: rs1322538046; hg19: chr1-248813461;