chr7-99876804-A-G

Position:

• chr7-99876804-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001005276.1(OR2AE1):​c.230T>C​(p.Ile77Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,613,364 control chromosomes in the GnomAD database, including 229,798 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.60 (29150 hom., cov: 30)
  • Exomes 𝑓: 0.52 (200648 hom.)
• Consequence: OR2AE1 NM_001005276.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

Genes affected

OR2AE1 (HGNC:15087): (olfactory receptor family 2 subfamily AE member 1) 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.4334534E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2AE1	NM_001005276.1	c.230T>C	p.Ile77Thr	missense_variant	1/1	ENST00000316368.3	NP_001005276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2AE1	ENST00000316368.3	c.230T>C	p.Ile77Thr	missense_variant	1/1	6	NM_001005276.1	ENSP00000313936.2

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90607 AN: 151764 Hom.: 29098 Cov.: 30

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.545

GnomAD3 exomes AF: 0.509 AC: 127943 AN: 251396 Hom.: 34465 AF XY: 0.503 AC XY: 68275 AN XY: 135862

Gnomad AFR exome AF: 0.858

Gnomad AMR exome AF: 0.456

Gnomad ASJ exome AF: 0.442

Gnomad EAS exome AF: 0.287

Gnomad SAS exome AF: 0.463

Gnomad FIN exome AF: 0.541

Gnomad NFE exome AF: 0.525

Gnomad OTH exome AF: 0.484

GnomAD4 exome AF: 0.519 AC: 758023 AN: 1461482 Hom.: 200648 Cov.: 48 AF XY: 0.515 AC XY: 374506 AN XY: 727078

Gnomad4 AFR exome AF: 0.856

Gnomad4 AMR exome AF: 0.455

Gnomad4 ASJ exome AF: 0.444

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.463

Gnomad4 FIN exome AF: 0.543

Gnomad4 NFE exome AF: 0.525

Gnomad4 OTH exome AF: 0.510

GnomAD4 genome AF: 0.597 AC: 90714 AN: 151882 Hom.: 29150 Cov.: 30 AF XY: 0.590 AC XY: 43799 AN XY: 74182

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.542

Alfa AF: 0.527 Hom.: 42932

Bravo AF: 0.600

TwinsUK AF: 0.525 AC: 1946

ALSPAC AF: 0.527 AC: 2030

ESP6500AA AF: 0.837 AC: 3687

ESP6500EA AF: 0.522 AC: 4489

ExAC AF: 0.520 AC: 63178

Asia WGS AF: 0.455 AC: 1583 AN: 3478

EpiCase AF: 0.509

EpiControl AF: 0.508

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.8
DANN	Benign	0.68
DEOGEN2	Benign	0.00024	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	6.4e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.48	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.020
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.0060
MPC		0.043
ClinPred		0.0032	T
GERP RS		0.81
Varity_R		0.048
gMVP		0.056

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

Publications

LitVar

Other links and lift over

dbSNP: rs2572023; hg19: chr7-99474427; COSMIC: COSV60390250; COSMIC: COSV60390250;