11-58119219-C-T

Position:

chr11-58119219-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001005211.2(OR9I1):c.226G>A(p.Val76Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000083 in 1,613,790 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000090 ( 2 hom. )

Consequence

OR9I1
NM_001005211.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.201

Variant links:

Genes affected

OR9I1 (HGNC:14718): (olfactory receptor family 9 subfamily I 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]

OR9I1 links:

OR9Q1 (HGNC:14724): (olfactory receptor family 9 subfamily Q 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]

OR9Q1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031476736).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR9I1	NM_001005211.2 linkuse as main transcript	c.226G>A	p.Val76Ile	missense_variant	3/3	ENST00000641439.1	NP_001005211.1	Q8NGQ6A0A126GVJ4
OR9Q1	NM_001005212.4 linkuse as main transcript	c.-14-60212C>T		intron_variant		ENST00000335397.3	NP_001005212.1	Q8NGQ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR9I1	ENST00000641439.1 linkuse as main transcript	c.226G>A	p.Val76Ile	missense_variant	3/3		NM_001005211.2	ENSP00000493370.1	Q8NGQ6
OR9Q1	ENST00000335397.3 linkuse as main transcript	c.-14-60212C>T		intron_variant		6	NM_001005212.4	ENSP00000334934.3	Q8NGQ5
OR9I1	ENST00000641478.1 linkuse as main transcript	c.226G>A	p.Val76Ile	missense_variant	3/3			ENSP00000493104.1	Q8NGQ6

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000183

AC:

AN:

250702

Hom.:

AF XY:

0.000251

AC XY:

AN XY:

135488

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00141

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000896

AC:

131

AN:

1461614

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00138

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.000198

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.226G>A (p.V76I) alteration is located in exon 1 (coding exon 1) of the OR9I1 gene. This alteration results from a G to A substitution at nucleotide position 226, causing the valine (V) at amino acid position 76 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

T;T;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.79

.;.;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.031

T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.7

L;L;L

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.84

.;.;N

REVEL

Benign

0.13

Sift

Benign

0.077

.;.;T

Sift4G

Benign

0.15

.;.;T

Polyphen

1.0

D;D;D

Vest4

0.096

MutPred

0.32

Gain of glycosylation at S75 (P = 0.1274);Gain of glycosylation at S75 (P = 0.1274);Gain of glycosylation at S75 (P = 0.1274);

MVP

0.043

MPC

0.016

ClinPred

0.10

GERP RS

5.1

Varity_R

0.073

gMVP

0.064

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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