chr1-248626360-C-T

Variant names:

• chr1-248626360-C-T
• rs139227153
• NM_001001964.2:c.769G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001001964.2(OR2T11):​c.769G>A​(p.Val257Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000216 in 1,572,746 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V257L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000035 (1 hom., cov: 28)
  • Exomes 𝑓: 0.000020 (5 hom.)
• Consequence: OR2T11 NM_001001964.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.73
• Publications: 6 publications found

Genes affected

OR2T11 (HGNC:19574): (olfactory receptor family 2 subfamily T member 11) 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

ENSG00000229255 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.027867109).
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001964.2. 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
	OR2T11	NM_001001964.2	MANE Select	c.769G>A	p.Val257Met	missense	Exon 2 of 2	NP_001001964.1	Q8NH01

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T11	ENST00000641193.1	MANE Select	c.769G>A	p.Val257Met	missense	Exon 2 of 2	ENSP00000492951.1	Q8NH01
	ENSG00000229255	ENST00000450847.2	TSL:2	n.195+16306G>A		intron	N/A
	ENSG00000229255	ENST00000825060.1		n.242+16306G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000350 AC: 5 AN: 142784 Hom.: 1 Cov.: 28

Gnomad AFR AF: 0.0000555

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: 0.0000453

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000123 AC: 3 AN: 244580 AF XY: 0.00000755

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000593

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000560

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000203 AC: 29 AN: 1429962 Hom.: 5 Cov.: 37 AF XY: 0.0000211 AC XY: 15 AN XY: 711634

African (AFR) AF: 0.000293 AC: 9 AN: 30718

American (AMR) AF: 0.0000458 AC: 2 AN: 43674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25744

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38712

South Asian (SAS) AF: 0.0000711 AC: 6 AN: 84366

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00000917 AC: 10 AN: 1090396

Other (OTH) AF: 0.0000169 AC: 1 AN: 59168

GnomAD4 genome AF: 0.0000350 AC: 5 AN: 142784 Hom.: 1 Cov.: 28 AF XY: 0.0000431 AC XY: 3 AN XY: 69548

African (AFR) AF: 0.0000555 AC: 2 AN: 36048

American (AMR) AF: 0.00 AC: 0 AN: 14678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3410

East Asian (EAS) AF: 0.00 AC: 0 AN: 4976

South Asian (SAS) AF: 0.00 AC: 0 AN: 4514

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000453 AC: 3 AN: 66156

Other (OTH) AF: 0.00 AC: 0 AN: 1990

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.0000264

ExAC AF: 0.00000843 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	0.10
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	10
DANN	Benign	0.061
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.3	N
PhyloP100		-2.7
PrimateAI	Benign	0.24	T
Polyphen		0.058	B
MutPred		0.35		Gain of phosphorylation at Y256 (P = 0.1186)
ClinPred		0.050	T
GERP RS		1.1
Varity_R		0.026
gMVP		0.069
Mutation Taster		=100/0	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: rs139227153; hg19: chr1-248789661; COSMIC: COSV58185260;