11-6785585-A-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001004489.3(OR2AG1):c.548A>C(p.His183Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,614,080 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H183R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.011 ( 40 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 37 hom. )

Consequence

OR2AG1
NM_001004489.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.19

Variant links:

Genes affected

OR2AG1 (HGNC:15142): (olfactory receptor family 2 subfamily AG 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. 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, Jul 2015]

OR2AG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002759248).

BP6

Variant 11-6785585-A-C is Benign according to our data. Variant chr11-6785585-A-C is described in ClinVar as [Benign]. Clinvar id is 776577.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0112 (1709/152208) while in subpopulation AFR AF= 0.0387 (1607/41542). AF 95% confidence interval is 0.0371. There are 40 homozygotes in gnomad4. There are 793 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 40 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2AG1	NM_001004489.3 link	c.548A>C	p.His183Pro	missense_variant	Exon 2 of 2	ENST00000641258.1	NP_001004489.1	Q9H205A0A126GVD0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2AG1	ENST00000641258.1 link	c.548A>C	p.His183Pro	missense_variant	Exon 2 of 2		NM_001004489.3	ENSP00000493074.1		Q9H205
OR2AG1	ENST00000641344.1 link	n.837+183A>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1700

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00959

GnomAD3 exomes

AF:

0.00301

AC:

756

AN:

251374

Hom.:

AF XY:

0.00211

AC XY:

287

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.0405

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000281

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.00123

AC:

1805

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

797

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0402

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000147

Gnomad4 OTH exome

AF:

0.00272

GnomAD4 genome

AF:

0.0112

AC:

1709

AN:

152208

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

793

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0387

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00949

Alfa

AF:

0.00344

Hom.:

Bravo

AF:

0.0129

ESP6500AA

AF:

0.0386

AC:

170

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.00390

AC:

473

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.6

DANN

Benign

0.22

DEOGEN2

Benign

0.0026

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.00075

LIST_S2

Benign

0.10

.;T

MetaRNN

Benign

0.0028

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.9

N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

2.4

.;N

REVEL

Benign

0.18

Sift

Benign

0.43

.;T

Polyphen

0.0

B;B

Vest4

0.12

MVP

0.32

MPC

0.039

ClinPred

0.0076

GERP RS

4.2

Varity_R

0.15

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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