dbSNP rs1186903: GABRR1:c.-242+3423C>T (chr6-89217852-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001267582.2(GABRR1):c.-242+3423C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,946 control chromosomes in the GnomAD database, including 10,798 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 0.37 ( 10746 hom., cov: 31)

Exomes 𝑓: 0.31 ( 52 hom. )

Consequence

GABRR1
NM_001267582.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.179

Publications

3 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=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001267582.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
GABRR1	NM_001267582.2	c.-242+3423C>T	intron	N/A	NP_001254511.1
GABRR1	NM_001256703.1	c.-530C>T	upstream_gene	N/A	NP_001243632.1
GABRR1	NM_001256704.1	c.-893C>T	upstream_gene	N/A	NP_001243633.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GABRR1	ENST00000369451.7	TSL:5	c.-239+3423C>T	intron	N/A	ENSP00000358463.3
GABRR1	ENST00000435811.5	TSL:2	c.-530C>T	upstream_gene	N/A	ENSP00000394687.1
GABRR1	ENST00000457434.1	TSL:5	n.-530C>T	upstream_gene	N/A	ENSP00000410130.1

Frequencies

GnomAD3 genomes

AF:

0.366

AC:

55561

AN:

151744

Hom.:

10739

Cov.:

show subpopulations

Gnomad AFR

AF:

0.461

Gnomad AMI

AF:

0.374

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.0946

Gnomad SAS

AF:

0.284

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.370

Gnomad OTH

AF:

0.335

GnomAD4 exome

AF:

0.312

AC:

338

AN:

1084

Hom.:

AF XY:

0.300

AC XY:

181

AN XY:

604

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.171

AC:

AN:

146

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.0625

AC:

AN:

South Asian (SAS)

AF:

0.232

AC:

AN:

European-Finnish (FIN)

AF:

0.563

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.348

AC:

276

AN:

794

Other (OTH)

AF:

0.239

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.366

AC:

55592

AN:

151862

Hom.:

10746

Cov.:

AF XY:

0.360

AC XY:

26744

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.461

AC:

19071

AN:

41384

American (AMR)

AF:

0.235

AC:

3594

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

863

AN:

3458

East Asian (EAS)

AF:

0.0944

AC:

489

AN:

5180

South Asian (SAS)

AF:

0.283

AC:

1360

AN:

4810

European-Finnish (FIN)

AF:

0.372

AC:

3918

AN:

10528

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.370

AC:

25159

AN:

67926

Other (OTH)

AF:

0.333

AC:

703

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1780

3561

5341

7122

8902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<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:

0.369

Hom.:

5266

Bravo

AF:

0.358

Asia WGS

AF:

0.265

AC:

923

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.0

(source)

DANN

Benign

0.56

PhyloP100

0.18

PromoterAI

0.0030

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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