Genetic Variant GABRR1:c.123-2302G>A (chr6-89205787-C-T) – 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.123-2302G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 152,068 control chromosomes in the GnomAD database, including 53,396 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 0.84 ( 53391 hom., cov: 30)

Exomes 𝑓: 0.86 ( 5 hom. )

Consequence

GABRR1
NM_002042.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.827

Publications

2 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002042.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GABRR1	NM_002042.5	MANE Select	c.123-2302G>A	intron	N/A	NP_002033.2	P24046-1
GABRR1	NM_001256703.1		c.123-4522G>A	intron	N/A	NP_001243632.1	P24046-2
GABRR1	NM_001256704.1		c.-241-1093G>A	intron	N/A	NP_001243633.1	P24046-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GABRR1	ENST00000454853.7	TSL:1 MANE Select	c.123-2302G>A	intron	N/A	ENSP00000412673.2	P24046-1
GABRR1	ENST00000435811.5	TSL:2	c.123-4522G>A	intron	N/A	ENSP00000394687.1	P24046-2
GABRR1	ENST00000369451.7	TSL:5	c.-238-1093G>A	intron	N/A	ENSP00000358463.3	P24046-3

Frequencies

GnomAD3 genomes

AF:

0.836

AC:

127019

AN:

151934

Hom.:

53345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.766

Gnomad AMI

AF:

0.816

Gnomad AMR

AF:

0.871

Gnomad ASJ

AF:

0.879

Gnomad EAS

AF:

0.905

Gnomad SAS

AF:

0.806

Gnomad FIN

AF:

0.901

Gnomad MID

AF:

0.867

Gnomad NFE

AF:

0.856

Gnomad OTH

AF:

0.831

GnomAD4 exome

AF:

0.857

AC:

AN:

Hom.:

Cov.:

AF XY:

0.833

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.833

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.836

AC:

127123

AN:

152054

Hom.:

53391

Cov.:

AF XY:

0.838

AC XY:

62325

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.766

AC:

31739

AN:

41452

American (AMR)

AF:

0.871

AC:

13300

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.879

AC:

3044

AN:

3462

East Asian (EAS)

AF:

0.905

AC:

4671

AN:

5162

South Asian (SAS)

AF:

0.807

AC:

3889

AN:

4820

European-Finnish (FIN)

AF:

0.901

AC:

9524

AN:

10574

Middle Eastern (MID)

AF:

0.874

AC:

257

AN:

294

European-Non Finnish (NFE)

AF:

0.856

AC:

58199

AN:

67998

Other (OTH)

AF:

0.833

AC:

1757

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1040

2080

3120

4160

5200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

884

1768

2652

3536

4420

<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:

0.851

Hom.:

92653

Bravo

AF:

0.833

Asia WGS

AF:

0.826

AC:

2873

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.70

(source)

DANN

Benign

0.47

PhyloP100

-0.83

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over