17-3292042-A-G

Position:

chr17-3292042-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002550.3(OR3A1):c.541T>C(p.Tyr181His) variant causes a missense change. The variant allele was found at a frequency of 0.00171 in 1,614,238 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0067 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 10 hom. )

Consequence

OR3A1
NM_002550.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.07

Variant links:

Genes affected

OR3A1 (HGNC:8282): (olfactory receptor family 3 subfamily A 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]

OR3A1 links:

OR3A2 (HGNC:8283): (olfactory receptor family 3 subfamily A member 2) 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]

OR3A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010933787).

BP6

Variant 17-3292042-A-G is Benign according to our data. Variant chr17-3292042-A-G is described in ClinVar as [Benign]. Clinvar id is 777091.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00667 (1016/152344) while in subpopulation AFR AF= 0.02 (832/41574). AF 95% confidence interval is 0.0189. There are 10 homozygotes in gnomad4. There are 469 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OR3A1	NM_002550.3 linkuse as main transcript	c.541T>C	p.Tyr181His	missense_variant	2/2	ENST00000323404.2
OR3A2	NM_002551.5 linkuse as main transcript	c.-278-7491T>C		intron_variant		ENST00000573901.3
OR3A2	XM_047436157.1 linkuse as main transcript	c.-255+7064T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
OR3A1	ENST00000323404.2 linkuse as main transcript	c.541T>C	p.Tyr181His	missense_variant	2/2		NM_002550.3	P1
OR3A2	ENST00000573901.3 linkuse as main transcript	c.-278-7491T>C		intron_variant		3	NM_002551.5	P1
OR3A2	ENST00000573491.5 linkuse as main transcript	c.-84-12889T>C		intron_variant		3
OR3A2	ENST00000576166.2 linkuse as main transcript	c.-84-12889T>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00662

AC:

1007

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0199

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00550

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00243

AC:

611

AN:

251488

Hom.:

AF XY:

0.00197

AC XY:

268

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0211

Gnomad AMR exome

AF:

0.00384

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000835

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00119

AC:

1738

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

802

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0190

Gnomad4 AMR exome

AF:

0.00385

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000562

Gnomad4 OTH exome

AF:

0.00358

GnomAD4 genome

AF:

0.00667

AC:

1016

AN:

152344

Hom.:

Cov.:

AF XY:

0.00629

AC XY:

469

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0200

Gnomad4 AMR

AF:

0.00549

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00109

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00376

Hom.:

Bravo

AF:

0.00743

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0207

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00273

AC:

331

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.00130

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 02, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.44

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

T;.

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

D;D

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

0.82

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-4.3

D;.

REVEL

Benign

0.17

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.51

MVP

0.68

MPC

0.21

ClinPred

0.030

GERP RS

5.0

Varity_R

0.89

gMVP

0.27

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over