Variant 17-3397984-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_003553.3(OR1E1):c.427G>A(p.Ala143Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 1,613,398 control chromosomes in the GnomAD database, including 714 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 0.021 ( 64 hom., cov: 32)

Exomes 𝑓: 0.028 ( 650 hom. )

Consequence

OR1E1
NM_003553.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.00

Variant links:

Genes affected

OR1E1 (HGNC:8189): (olfactory receptor family 1 subfamily E 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]

OR1E1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012420684).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0208 (3159/151684) while in subpopulation NFE AF= 0.0322 (2189/68000). AF 95% confidence interval is 0.0311. There are 64 homozygotes in gnomad4. There are 1378 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR1E1	NM_003553.3 link	c.427G>A	p.Ala143Thr	missense_variant	1/1	ENST00000322608.2	NP_003544.2	P30953

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR1E1	ENST00000322608.2 link	c.427G>A	p.Ala143Thr	missense_variant	1/1	6	NM_003553.3	ENSP00000313384.2		P30953

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3159

AN:

151568

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00665

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00540

Gnomad FIN

AF:

0.0185

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0322

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0208

AC:

5228

AN:

251100

Hom.:

AF XY:

0.0215

AC XY:

2922

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.00602

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.00714

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00487

Gnomad FIN exome

AF:

0.0220

Gnomad NFE exome

AF:

0.0334

Gnomad OTH exome

AF:

0.0258

GnomAD4 exome

AF:

0.0280

AC:

40996

AN:

1461714

Hom.:

650

Cov.:

AF XY:

0.0275

AC XY:

20009

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00492

Gnomad4 AMR exome

AF:

0.0152

Gnomad4 ASJ exome

AF:

0.00704

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00509

Gnomad4 FIN exome

AF:

0.0212

Gnomad4 NFE exome

AF:

0.0332

Gnomad4 OTH exome

AF:

0.0233

GnomAD4 genome

AF:

0.0208

AC:

3159

AN:

151684

Hom.:

Cov.:

AF XY:

0.0186

AC XY:

1378

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.00663

Gnomad4 AMR

AF:

0.0166

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00540

Gnomad4 FIN

AF:

0.0185

Gnomad4 NFE

AF:

0.0322

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.0158

Hom.:

Bravo

AF:

0.0210

TwinsUK

AF:

0.0345

AC:

128

ALSPAC

AF:

0.0278

AC:

107

ESP6500AA

AF:

0.00658

AC:

ESP6500EA

AF:

0.0329

AC:

283

ExAC

AF:

0.0215

AC:

2609

EpiCase

AF:

0.0335

EpiControl

AF:

0.0339

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.057

DANN

Benign

0.94

DEOGEN2

Benign

0.015

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.21

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.18

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.22

REVEL

Benign

0.055

Sift

Benign

0.088

Sift4G

Uncertain

0.026

Polyphen

0.013

Vest4

0.0060

MPC

0.32

ClinPred

0.013

GERP RS

-2.3

Varity_R

0.041

gMVP

0.077

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over