chr1-247921382-C-T

Variant names:

• chr1-247921382-C-T
• rs1441322897
• NM_001005522.2:c.365C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001005522.2(OR2T8):​c.365C>T​(p.Ala122Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000923 in 1,300,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 5)
  • Exomes 𝑓: 0.0000092 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T8 NM_001005522.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.525
• Publications: 1 publications found

Genes affected

OR2T8 (HGNC:15020): (olfactory receptor family 2 subfamily T member 8) 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061716884).
• BP6: Variant 1-247921382-C-T is Benign according to our data. Variant chr1-247921382-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2282861.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005522.2. 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
	OR2T8	NM_001005522.2	MANE Select	c.365C>T	p.Ala122Val	missense	Exon 2 of 2	NP_001005522.1	A6NH00

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T8	ENST00000641945.2	MANE Select	c.365C>T	p.Ala122Val	missense	Exon 2 of 2	ENSP00000493286.1	A6NH00

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 29458 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: 0.0000126 AC: 1 AN: 79660 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.0000342

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000923 AC: 12 AN: 1300368 Hom.: 0 Cov.: 21 AF XY: 0.00000773 AC XY: 5 AN XY: 647042

African (AFR) AF: 0.00 AC: 0 AN: 30492

American (AMR) AF: 0.00 AC: 0 AN: 40282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24848

East Asian (EAS) AF: 0.00 AC: 0 AN: 38468

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 78374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3834

European-Non Finnish (NFE) AF: 0.0000112 AC: 11 AN: 983964

Other (OTH) AF: 0.00 AC: 0 AN: 55080

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 29458 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 12454

African (AFR) AF: 0.00 AC: 0 AN: 9376

American (AMR) AF: 0.00 AC: 0 AN: 2382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 742

East Asian (EAS) AF: 0.00 AC: 0 AN: 1032

South Asian (SAS) AF: 0.00 AC: 0 AN: 796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1056

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 134

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 13332

Other (OTH) AF: 0.00 AC: 0 AN: 434

Alfa AF: 0.0000483 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.071
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.36
DANN	Benign	0.24
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00074	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-2.5	N
PhyloP100		0.53
PrimateAI	Benign	0.21	T
PROVEAN	Benign	3.3	N
REVEL	Benign	0.031
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.086
MutPred		0.46		Loss of methylation at R120 (P = 0.1065)
MVP		0.22
ClinPred		0.048	T
GERP RS		0.049
Varity_R		0.018
gMVP		0.030
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: rs1441322897; hg19: chr1-248084684;