Genetic Variant NM_002042.5:c.80A>G (chr6-89217243-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002042.5(GABRR1):c.80A>G(p.His27Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,613,658 control chromosomes in the GnomAD database, including 55,646 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.23 ( 4286 hom., cov: 31)

Exomes 𝑓: 0.26 ( 51360 hom. )

Consequence

GABRR1
NM_002042.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.80

Publications

35 publications found

Variant links:

Genes affected

GABRR1 (HGNC:4090): (gamma-aminobutyric acid type A receptor subunit rho1) GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA receptors, which are ligand-gated chloride channels. GABRR1 is a member of the rho subunit family. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

GABRR1 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=0.0044744313).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR1	NM_002042.5 link	c.80A>G	p.His27Arg	missense_variant	Exon 1 of 10	ENST00000454853.7	NP_002033.2	P24046-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000454853.7 link	c.80A>G	p.His27Arg	missense_variant	Exon 1 of 10	1	NM_002042.5	ENSP00000412673.2		P24046-1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34206

AN:

151988

Hom.:

4274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.240

Gnomad AMR

AF:

0.320

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.285

Gnomad FIN

AF:

0.214

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.236

GnomAD2 exomes

AF:

0.268

AC:

67282

AN:

251290

AF XY:

0.270

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.384

Gnomad ASJ exome

AF:

0.336

Gnomad EAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.208

Gnomad NFE exome

AF:

0.257

Gnomad OTH exome

AF:

0.281

GnomAD4 exome

AF:

0.261

AC:

381867

AN:

1461552

Hom.:

51360

Cov.:

AF XY:

0.262

AC XY:

190726

AN XY:

727088

show subpopulations

African (AFR)

AF:

0.104

AC:

3497

AN:

33478

American (AMR)

AF:

0.372

AC:

16619

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

8595

AN:

26132

East Asian (EAS)

AF:

0.247

AC:

9789

AN:

39688

South Asian (SAS)

AF:

0.287

AC:

24755

AN:

86240

European-Finnish (FIN)

AF:

0.205

AC:

10938

AN:

53414

Middle Eastern (MID)

AF:

0.248

AC:

1428

AN:

5768

European-Non Finnish (NFE)

AF:

0.261

AC:

290535

AN:

1111752

Other (OTH)

AF:

0.260

AC:

15711

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

13864

27728

41591

55455

69319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9830

19660

29490

39320

49150

<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:

0.225

AC:

34245

AN:

152106

Hom.:

4286

Cov.:

AF XY:

0.224

AC XY:

16635

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.109

AC:

4521

AN:

41504

American (AMR)

AF:

0.321

AC:

4905

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

1187

AN:

3472

East Asian (EAS)

AF:

0.277

AC:

1432

AN:

5170

South Asian (SAS)

AF:

0.287

AC:

1378

AN:

4806

European-Finnish (FIN)

AF:

0.214

AC:

2267

AN:

10576

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.261

AC:

17757

AN:

67978

Other (OTH)

AF:

0.240

AC:

508

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1332

2664

3997

5329

6661

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.252

Hom.:

11981

Bravo

AF:

0.232

TwinsUK

AF:

0.260

AC:

963

ALSPAC

AF:

0.264

AC:

1016

ESP6500AA

AF:

0.107

AC:

472

ESP6500EA

AF:

0.269

AC:

2313

ExAC

AF:

0.261

AC:

31689

Asia WGS

AF:

0.240

AC:

835

AN:

3478

EpiCase

AF:

0.267

EpiControl

AF:

0.268

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.028

T;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.58

T;T

MetaRNN

Benign

0.0045

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

PhyloP100

1.8

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.26

N;N

REVEL

Benign

0.025

Sift

Uncertain

0.0070

D;T

Sift4G

Pathogenic

0.0

D;T

Polyphen

0.021

B;B

Vest4

0.038

MPC

0.31

ClinPred

0.013

GERP RS

1.8

PromoterAI

0.021

Neutral

(source)

Varity_R

0.068

gMVP

0.17

Mutation Taster

=94/6

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