chr6-29588087-C-T

Variant names:

Variant summary

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

The NM_007160.4(OR2H2):c.143C>T(p.Ala48Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 949,472 control chromosomes in the GnomAD database, including 41,583 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 5631 hom., cov: 31)

Exomes 𝑓: 0.29 ( 35952 hom. )

Consequence

OR2H2
NM_007160.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.787

Publications

23 publications found

Variant links:

Genes affected

OR2H2 (HGNC:8253): (olfactory receptor family 2 subfamily H 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]

OR2H2 links:

GABBR1 (HGNC:4070): (gamma-aminobutyric acid type B receptor subunit 1) This gene encodes a receptor for gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the mammalian central nervous system. This receptor functions as a heterodimer with GABA(B) receptor 2. Defects in this gene may underlie brain disorders such as schizophrenia and epilepsy. Alternative splicing generates multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jan 2016]

GABBR1 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with language delay and variable cognitive abnormalities
Inheritance: AD Classification: MODERATE Submitted by: G2P

GABBR1 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 (MetaRNN=1.8432736E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2H2	NM_007160.4 link	c.143C>T	p.Ala48Val	missense_variant	Exon 2 of 2	ENST00000641840.1	NP_009091.3	O95918A0A1U9X844

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR2H2	ENST00000641840.1 link	c.143C>T	p.Ala48Val	missense_variant	Exon 2 of 2		NM_007160.4	ENSP00000492959.1	O95918
OR2H2	ENST00000383640.4 link	c.143C>T	p.Ala48Val	missense_variant	Exon 1 of 1	6		ENSP00000373136.2	O95918
GABBR1	ENST00000355973.7 link	c.*2+15454G>A		intron_variant	Intron 18 of 18	2		ENSP00000348248.3	Q9UBS5-2

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40603

AN:

151766

Hom.:

5623

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.236

Gnomad AMR

AF:

0.315

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.376

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.292

GnomAD2 exomes

AF:

0.302

AC:

74755

AN:

247266

AF XY:

0.301

show subpopulations

Gnomad AFR exome

AF:

0.264

Gnomad AMR exome

AF:

0.402

Gnomad ASJ exome

AF:

0.291

Gnomad EAS exome

AF:

0.451

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.262

Gnomad OTH exome

AF:

0.302

GnomAD4 exome

AF:

0.290

AC:

231667

AN:

797588

Hom.:

35952

Cov.:

AF XY:

0.292

AC XY:

123599

AN XY:

422850

show subpopulations

African (AFR)

AF:

0.266

AC:

5709

AN:

21430

American (AMR)

AF:

0.391

AC:

17191

AN:

43920

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

6607

AN:

22030

East Asian (EAS)

AF:

0.503

AC:

18534

AN:

36872

South Asian (SAS)

AF:

0.354

AC:

25967

AN:

73444

European-Finnish (FIN)

AF:

0.198

AC:

10344

AN:

52222

Middle Eastern (MID)

AF:

0.417

AC:

1879

AN:

4506

European-Non Finnish (NFE)

AF:

0.266

AC:

134195

AN:

504468

Other (OTH)

AF:

0.290

AC:

11241

AN:

38696

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

10456

20912

31368

41824

52280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2808

5616

8424

11232

14040

<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:

0.267

AC:

40628

AN:

151884

Hom.:

5631

Cov.:

AF XY:

0.270

AC XY:

20072

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.260

AC:

10768

AN:

41406

American (AMR)

AF:

0.315

AC:

4806

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.289

AC:

1002

AN:

3468

East Asian (EAS)

AF:

0.466

AC:

2392

AN:

5130

South Asian (SAS)

AF:

0.376

AC:

1806

AN:

4798

European-Finnish (FIN)

AF:

0.193

AC:

2042

AN:

10558

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.248

AC:

16866

AN:

67956

Other (OTH)

AF:

0.292

AC:

614

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1523

3047

4570

6094

7617

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<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:

0.265

Hom.:

5068

Bravo

AF:

0.280

TwinsUK

AF:

0.237

AC:

880

ALSPAC

AF:

0.242

AC:

932

ESP6500AA

AF:

0.260

AC:

786

ESP6500EA

AF:

0.253

AC:

1371

ExAC

AF:

0.300

AC:

35604

Asia WGS

AF:

0.356

AC:

1236

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.8

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.0018

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0046

MetaRNN

Benign

0.00018

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.78

N;N

PhyloP100

-0.79

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.21

.;N

REVEL

Benign

0.045

Sift

Benign

0.50

.;T

Sift4G

Benign

0.50

.;T

Polyphen

0.0

B;B

Vest4

0.025

MPC

0.18

ClinPred

0.0021

GERP RS

2.0

Varity_R

0.031

gMVP

0.053

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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