Genetic Variant NM_002042.5:c.1185G>A (chr6-89179025-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_002042.5(GABRR1):c.1185G>A(p.Ala395Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,613,682 control chromosomes in the GnomAD database, including 111,594 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 0.40 ( 12702 hom., cov: 31)

Exomes 𝑓: 0.36 ( 98892 hom. )

Consequence

GABRR1
NM_002042.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.31

Publications

18 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP7

Synonymous conserved (PhyloP=2.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR1	NM_002042.5 link	c.1185G>A	p.Ala395Ala	synonymous_variant	Exon 10 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.1185G>A	p.Ala395Ala	synonymous_variant	Exon 10 of 10	1	NM_002042.5	ENSP00000412673.2		P24046-1

Frequencies

GnomAD3 genomes

AF:

0.401

AC:

60822

AN:

151826

Hom.:

12697

Cov.:

show subpopulations

Gnomad AFR

AF:

0.465

Gnomad AMI

AF:

0.377

Gnomad AMR

AF:

0.390

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.639

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.504

Gnomad MID

AF:

0.315

Gnomad NFE

AF:

0.339

Gnomad OTH

AF:

0.375

GnomAD2 exomes

AF:

0.392

AC:

98348

AN:

251054

AF XY:

0.384

show subpopulations

Gnomad AFR exome

AF:

0.466

Gnomad AMR exome

AF:

0.396

Gnomad ASJ exome

AF:

0.281

Gnomad EAS exome

AF:

0.648

Gnomad FIN exome

AF:

0.496

Gnomad NFE exome

AF:

0.337

Gnomad OTH exome

AF:

0.351

GnomAD4 exome

AF:

0.362

AC:

529478

AN:

1461738

Hom.:

98892

Cov.:

AF XY:

0.360

AC XY:

262114

AN XY:

727178

show subpopulations

African (AFR)

AF:

0.467

AC:

15645

AN:

33480

American (AMR)

AF:

0.395

AC:

17667

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

7351

AN:

26134

East Asian (EAS)

AF:

0.627

AC:

24895

AN:

39700

South Asian (SAS)

AF:

0.365

AC:

31454

AN:

86256

European-Finnish (FIN)

AF:

0.492

AC:

26260

AN:

53364

Middle Eastern (MID)

AF:

0.264

AC:

1521

AN:

5766

European-Non Finnish (NFE)

AF:

0.344

AC:

382380

AN:

1111934

Other (OTH)

AF:

0.369

AC:

22305

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

19864

39729

59593

79458

99322

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12538

25076

37614

50152

62690

<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:

0.401

AC:

60879

AN:

151944

Hom.:

12702

Cov.:

AF XY:

0.410

AC XY:

30482

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.465

AC:

19271

AN:

41460

American (AMR)

AF:

0.390

AC:

5959

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

990

AN:

3466

East Asian (EAS)

AF:

0.639

AC:

3282

AN:

5138

South Asian (SAS)

AF:

0.378

AC:

1822

AN:

4818

European-Finnish (FIN)

AF:

0.504

AC:

5310

AN:

10534

Middle Eastern (MID)

AF:

0.318

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.339

AC:

23014

AN:

67934

Other (OTH)

AF:

0.376

AC:

794

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1836

3671

5507

7342

9178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

582

1164

1746

2328

2910

<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:

0.357

Hom.:

27498

Bravo

AF:

0.395

Asia WGS

AF:

0.477

AC:

1659

AN:

3478

EpiCase

AF:

0.335

EpiControl

AF:

0.332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

7.9

(source)

DANN

Benign

0.44

PhyloP100

2.3

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