1-248488626-A-G

Position:

• chr1-248488626-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001004697.2(OR2T5):​c.38A>G​(p.Lys13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.68 (12178 hom., cov: 7)
  • Exomes 𝑓: 0.86 (426646 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T5 NM_001004697.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.17

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]

LOC105373277 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.0693344E-6).
• BP6: Variant 1-248488626-A-G is Benign according to our data. Variant chr1-248488626-A-G is described in ClinVar as [Benign]. Clinvar id is 403273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2T5	NM_001004697.2	c.38A>G	p.Lys13Arg	missense_variant	1/1	ENST00000641363.1
LOC105373277	XR_002958498.2	n.188-3142T>C		intron_variant, non_coding_transcript_variant
LOC105373277	XR_001738575.2	n.144-3142T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2T5	ENST00000641363.1	c.38A>G	p.Lys13Arg	missense_variant	1/1		NM_001004697.2	P1

Frequencies

GnomAD3 genomes AF: 0.682 AC: 31906 AN: 46790 Hom.: 12165 Cov.: 7

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.740

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.674

GnomAD3 exomes AF: 0.711 AC: 80058 AN: 112530 Hom.: 39156 AF XY: 0.703 AC XY: 41793 AN XY: 59416

Gnomad AFR exome AF: 0.874

Gnomad AMR exome AF: 0.740

Gnomad ASJ exome AF: 0.790

Gnomad EAS exome AF: 0.997

Gnomad SAS exome AF: 0.861

Gnomad FIN exome AF: 0.624

Gnomad NFE exome AF: 0.608

Gnomad OTH exome AF: 0.718

GnomAD4 exome AF: 0.863 AC: 950124 AN: 1101054 Hom.: 426646 Cov.: 20 AF XY: 0.867 AC XY: 480448 AN XY: 554254

Gnomad4 AFR exome AF: 0.961

Gnomad4 AMR exome AF: 0.908

Gnomad4 ASJ exome AF: 0.925

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.960

Gnomad4 FIN exome AF: 0.792

Gnomad4 NFE exome AF: 0.845

Gnomad4 OTH exome AF: 0.882

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.682 AC: 31931 AN: 46812 Hom.: 12178 Cov.: 7 AF XY: 0.683 AC XY: 15569 AN XY: 22792

Gnomad4 AFR AF: 0.628

Gnomad4 AMR AF: 0.707

Gnomad4 ASJ AF: 0.808

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.802

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.678

Alfa AF: 0.744 Hom.: 3329

ExAC AF: 0.736 AC: 80646

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.80
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00092	N
MetaRNN	Benign	0.0000021	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.97	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.19	T
Polyphen		0.0	B
ClinPred		0.0051	T
GERP RS		-1.3
Varity_R		0.032
gMVP		0.045

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1770043; hg19: chr1-248651927; COSMIC: COSV63540373; COSMIC: COSV63540373;