Genetic Variant OR4X1:c.-112A>G (chr11-48263749-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001004726.1(OR4X1):c.-112A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 778,014 control chromosomes in the GnomAD database, including 201,722 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.67 ( 35696 hom., cov: 32)

Exomes 𝑓: 0.72 ( 166026 hom. )

Consequence

OR4X1
NM_001004726.1 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0880

Publications

5 publications found

Variant links:

Genes affected

OR4X1 (HGNC:14854): (olfactory receptor family 4 subfamily X 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]

OR4X1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4X1	NM_001004726.1 link	c.-112A>G		upstream_gene_variant		ENST00000320048.1	NP_001004726.1	Q8NH49

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4X1	ENST00000320048.1 link	c.-112A>G		upstream_gene_variant		6	NM_001004726.1	ENSP00000321506.1		Q8NH49

Frequencies

GnomAD3 genomes

AF:

0.674

AC:

102497

AN:

151976

Hom.:

35686

Cov.:

show subpopulations

Gnomad AFR

AF:

0.505

Gnomad AMI

AF:

0.835

Gnomad AMR

AF:

0.733

Gnomad ASJ

AF:

0.694

Gnomad EAS

AF:

0.577

Gnomad SAS

AF:

0.544

Gnomad FIN

AF:

0.811

Gnomad MID

AF:

0.674

Gnomad NFE

AF:

0.757

Gnomad OTH

AF:

0.669

GnomAD4 exome

AF:

0.723

AC:

452514

AN:

625920

Hom.:

166026

AF XY:

0.716

AC XY:

233471

AN XY:

326252

show subpopulations

African (AFR)

AF:

0.501

AC:

7994

AN:

15970

American (AMR)

AF:

0.775

AC:

17634

AN:

22754

Ashkenazi Jewish (ASJ)

AF:

0.691

AC:

10633

AN:

15386

East Asian (EAS)

AF:

0.635

AC:

21329

AN:

33568

South Asian (SAS)

AF:

0.541

AC:

28136

AN:

51972

European-Finnish (FIN)

AF:

0.794

AC:

34122

AN:

42958

Middle Eastern (MID)

AF:

0.630

AC:

2286

AN:

3630

European-Non Finnish (NFE)

AF:

0.756

AC:

308230

AN:

407874

Other (OTH)

AF:

0.696

AC:

22150

AN:

31808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

6653

13306

19960

26613

33266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3940

7880

11820

15760

19700

<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:

0.674

AC:

102544

AN:

152094

Hom.:

35696

Cov.:

AF XY:

0.674

AC XY:

50094

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.505

AC:

20938

AN:

41474

American (AMR)

AF:

0.733

AC:

11197

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.694

AC:

2404

AN:

3464

East Asian (EAS)

AF:

0.578

AC:

2986

AN:

5168

South Asian (SAS)

AF:

0.545

AC:

2619

AN:

4808

European-Finnish (FIN)

AF:

0.811

AC:

8589

AN:

10594

Middle Eastern (MID)

AF:

0.670

AC:

197

AN:

294

European-Non Finnish (NFE)

AF:

0.757

AC:

51439

AN:

67990

Other (OTH)

AF:

0.670

AC:

1415

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1640

3280

4919

6559

8199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

800

1600

2400

3200

4000

<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:

0.706

Hom.:

6049

Bravo

AF:

0.665

Asia WGS

AF:

0.510

AC:

1773

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.0

(source)

DANN

Benign

0.76

PhyloP100

0.088

PromoterAI

0.0042

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over