Genetic Variant NM_001004711.2:c.326G>T (chr11-59515238-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004711.2(OR4D9):c.326G>T(p.Gly109Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,613,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G109E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

OR4D9
NM_001004711.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.106

Publications

2 publications found

Variant links:

Genes affected

OR4D9 (HGNC:15178): (olfactory receptor family 4 subfamily D member 9) 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]

OR4D9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18541586).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004711.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4D9	NM_001004711.2	MANE Select	c.326G>T	p.Gly109Val	missense	Exon 3 of 3	NP_001004711.1	A0A126GVP8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4D9	ENST00000641962.1	MANE Select	c.326G>T	p.Gly109Val	missense	Exon 3 of 3	ENSP00000493010.1	Q8NGE8
	OR4D9	ENST00000641278.1		c.326G>T	p.Gly109Val	missense	Exon 3 of 3	ENSP00000493042.1	Q8NGE8

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152074

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000399

AC:

AN:

250840

AF XY:

0.0000516

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000705

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000170

AC:

248

AN:

1461342

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

114

AN XY:

727040

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33350

American (AMR)

AF:

0.00

AC:

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86188

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000194

AC:

216

AN:

1111882

Other (OTH)

AF:

0.000480

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000658

AC:

AN:

152074

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41412

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.011

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.79

M_CAP

Benign

0.0068

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

0.11

PrimateAI

Benign

0.25

PROVEAN

Pathogenic

-7.0

REVEL

Benign

0.13

Sift

Uncertain

0.019

Sift4G

Uncertain

0.044

Polyphen

0.65

Vest4

0.22

MVP

0.58

MPC

0.13

ClinPred

0.19

GERP RS

3.2

Varity_R

0.38

gMVP

0.16

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over