Variant 6-89198141-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002042.5(GABRR1):c.451A>C(p.Lys151Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000417 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 0 hom. )

Consequence

GABRR1
NM_002042.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.23

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38617402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRR1	NM_002042.5 linkuse as main transcript	c.451A>C	p.Lys151Gln	missense_variant	5/10	ENST00000454853.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRR1	ENST00000454853.7 linkuse as main transcript	c.451A>C	p.Lys151Gln	missense_variant	5/10	1	NM_002042.5	P1	P24046-1
GABRR1	ENST00000435811.5 linkuse as main transcript	c.400A>C	p.Lys134Gln	missense_variant	4/9	2			P24046-2
GABRR1	ENST00000369451.7 linkuse as main transcript	c.190A>C	p.Lys64Gln	missense_variant	7/12	5			P24046-3
GABRR1	ENST00000457434.1 linkuse as main transcript	c.*412A>C		3_prime_UTR_variant, NMD_transcript_variant	6/11	5

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000247

AC:

AN:

251470

Hom.:

AF XY:

0.000287

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000492

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000436

AC:

637

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

294

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000497

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000539

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000237

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000465

Hom.:

Bravo

AF:

0.000212

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ExAC

AF:

0.000280

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000771

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2024

The c.451A>C (p.K151Q) alteration is located in exon 5 (coding exon 5) of the GABRR1 gene. This alteration results from a A to C substitution at nucleotide position 451, causing the lysine (K) at amino acid position 151 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.24

Cadd

Uncertain

Dann

Uncertain

0.98

DEOGEN2

Benign

0.12

T;.;.;.;.

Eigen

Benign

0.095

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

D;D;.;D;.

M_CAP

Benign

0.083

MetaRNN

Benign

0.39

T;T;T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

0.46

N;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.87

N;N;.;.;N

REVEL

Uncertain

0.32

Sift

Benign

0.13

T;T;.;.;T

Sift4G

Benign

0.30

T;T;T;T;T

Polyphen

0.60

P;B;.;.;.

Vest4

0.70

MVP

0.87

MPC

0.94

ClinPred

0.070

GERP RS

5.8

Varity_R

0.29

gMVP

0.47

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over