1-248650176-C-A

Variant names:

• chr1-248650176-C-A
• rs772347670
• NM_001001824.2:c.709G>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001001824.2(OR2T27):​c.709G>T​(p.Ala237Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,564,902 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000035 (0 hom., cov: 26)
  • Exomes 𝑓: 0.000019 (3 hom.)
• Consequence: OR2T27 NM_001001824.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.29
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.41777077).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.709G>T	p.Ala237Ser	missense	Exon 2 of 2	NP_001001824.1	Q8NH04
	OR2T27	NM_001386060.1		c.709G>T	p.Ala237Ser	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.709G>T	p.Ala237Ser	missense	Exon 2 of 2	ENSP00000493412.1	Q8NH04
	OR2T27	ENST00000641652.1		c.709G>T	p.Ala237Ser	missense	Exon 3 of 3	ENSP00000493434.1	Q8NH04

Frequencies

GnomAD3 genomes AF: 0.0000353 AC: 5 AN: 141776 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000705

Gnomad ASJ AF: 0.000896

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: 0.000514

GnomAD2 exomes AF: 0.0000418 AC: 10 AN: 239238 AF XY: 0.0000309

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000606

Gnomad EAS exome AF: 0.000116

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000926

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.0000190 AC: 27 AN: 1423012 Hom.: 3 Cov.: 33 AF XY: 0.0000127 AC XY: 9 AN XY: 708102

African (AFR) AF: 0.00 AC: 0 AN: 32700

American (AMR) AF: 0.0000232 AC: 1 AN: 43034

Ashkenazi Jewish (ASJ) AF: 0.000388 AC: 10 AN: 25804

East Asian (EAS) AF: 0.0000782 AC: 3 AN: 38380

South Asian (SAS) AF: 0.00 AC: 0 AN: 83660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5626

European-Non Finnish (NFE) AF: 0.00000831 AC: 9 AN: 1083586

Other (OTH) AF: 0.0000677 AC: 4 AN: 59046

GnomAD4 genome AF: 0.0000352 AC: 5 AN: 141890 Hom.: 0 Cov.: 26 AF XY: 0.0000726 AC XY: 5 AN XY: 68834

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

African (AFR) AF: 0.00 AC: 0 AN: 39162

American (AMR) AF: 0.0000704 AC: 1 AN: 14198

Ashkenazi Jewish (ASJ) AF: 0.000896 AC: 3 AN: 3348

East Asian (EAS) AF: 0.00 AC: 0 AN: 4654

South Asian (SAS) AF: 0.00 AC: 0 AN: 4194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64114

Other (OTH) AF: 0.000509 AC: 1 AN: 1966

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000494837), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000435 Hom.: 0

ExAC AF: 0.0000336 AC: 4

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	0.17
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0086	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	-0.0017
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.00089	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.3
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.12
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.043	D
Polyphen		1.0	D
Vest4		0.43
MutPred		0.59		Gain of disorder (P = 0.0288)
MVP		0.62
MPC		1.3
ClinPred		0.52	D
GERP RS		2.5
Varity_R		0.33
gMVP		0.043
Mutation Taster		=97/3	polymorphism

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: rs772347670; hg19: chr1-248813477;