dbSNP rs422751: GABRR1:p.Asp146Asp (chr6-89198154-G-A) – 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.438C>T(p.Asp146Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 1,613,662 control chromosomes in the GnomAD database, including 550,706 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 0.79 ( 48079 hom., cov: 29)

Exomes 𝑓: 0.83 ( 502627 hom. )

Consequence

GABRR1
NM_002042.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00400

Publications

22 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=-0.46).

BP7

Synonymous conserved (PhyloP=-0.004 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR1	NM_002042.5 link	c.438C>T	p.Asp146Asp	synonymous_variant	Exon 5 of 10	ENST00000454853.7	NP_002033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000454853.7 link	c.438C>T	p.Asp146Asp	synonymous_variant	Exon 5 of 10	1	NM_002042.5	ENSP00000412673.2

Frequencies

GnomAD3 genomes

AF:

0.791

AC:

120021

AN:

151802

Hom.:

48046

Cov.:

show subpopulations

Gnomad AFR

AF:

0.659

Gnomad AMI

AF:

0.811

Gnomad AMR

AF:

0.834

Gnomad ASJ

AF:

0.821

Gnomad EAS

AF:

0.957

Gnomad SAS

AF:

0.768

Gnomad FIN

AF:

0.911

Gnomad MID

AF:

0.793

Gnomad NFE

AF:

0.829

Gnomad OTH

AF:

0.793

GnomAD2 exomes

AF:

0.833

AC:

209412

AN:

251468

AF XY:

0.829

show subpopulations

Gnomad AFR exome

AF:

0.652

Gnomad AMR exome

AF:

0.885

Gnomad ASJ exome

AF:

0.807

Gnomad EAS exome

AF:

0.956

Gnomad FIN exome

AF:

0.912

Gnomad NFE exome

AF:

0.829

Gnomad OTH exome

AF:

0.829

GnomAD4 exome

AF:

0.828

AC:

1210130

AN:

1461742

Hom.:

502627

Cov.:

AF XY:

0.826

AC XY:

600332

AN XY:

727190

show subpopulations

African (AFR)

AF:

0.648

AC:

21707

AN:

33474

American (AMR)

AF:

0.880

AC:

39337

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.805

AC:

21045

AN:

26132

East Asian (EAS)

AF:

0.964

AC:

38258

AN:

39700

South Asian (SAS)

AF:

0.760

AC:

65599

AN:

86258

European-Finnish (FIN)

AF:

0.910

AC:

48592

AN:

53420

Middle Eastern (MID)

AF:

0.797

AC:

4599

AN:

5768

European-Non Finnish (NFE)

AF:

0.829

AC:

921508

AN:

1111872

Other (OTH)

AF:

0.819

AC:

49485

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

12671

25342

38012

50683

63354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21000

42000

63000

84000

105000

<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:

0.791

AC:

120110

AN:

151920

Hom.:

48079

Cov.:

AF XY:

0.796

AC XY:

59091

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.659

AC:

27251

AN:

41364

American (AMR)

AF:

0.834

AC:

12722

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.821

AC:

2852

AN:

3472

East Asian (EAS)

AF:

0.957

AC:

4949

AN:

5170

South Asian (SAS)

AF:

0.767

AC:

3684

AN:

4800

European-Finnish (FIN)

AF:

0.911

AC:

9628

AN:

10570

Middle Eastern (MID)

AF:

0.791

AC:

231

AN:

292

European-Non Finnish (NFE)

AF:

0.829

AC:

56374

AN:

67984

Other (OTH)

AF:

0.796

AC:

1679

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1204

2408

3613

4817

6021

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

870

1740

2610

3480

4350

<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:

0.803

Hom.:

90886

Bravo

AF:

0.782

Asia WGS

AF:

0.837

AC:

2912

AN:

3478

EpiCase

AF:

0.823

EpiControl

AF:

0.823

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

2.4

(source)

DANN

Benign

0.64

PhyloP100

-0.0040

Mutation Taster

=98/2

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