Variant 6-29603604-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001470.4(GABBR1):c.2825C>T(p.Pro942Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000699 in 1,431,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

GABBR1
NM_001470.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08

Variant links:

Genes affected

GABBR1 (HGNC:4070): (gamma-aminobutyric acid type B receptor subunit 1) This gene encodes a receptor for gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the mammalian central nervous system. This receptor functions as a heterodimer with GABA(B) receptor 2. Defects in this gene may underlie brain disorders such as schizophrenia and epilepsy. Alternative splicing generates multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jan 2016]

GABBR1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1430448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR1	NM_001470.4 linkuse as main transcript	c.2825C>T	p.Pro942Leu	missense_variant	23/23	ENST00000377034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR1	ENST00000377034.9 linkuse as main transcript	c.2825C>T	p.Pro942Leu	missense_variant	23/23	1	NM_001470.4	P1	Q9UBS5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1431258

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709946

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.10e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 10, 2022

The c.2825C>T (p.P942L) alteration is located in exon 23 (coding exon 22) of the GABBR1 gene. This alteration results from a C to T substitution at nucleotide position 2825, causing the proline (P) at amino acid position 942 to be replaced by a leucine (L). 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

Benign

0.069

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.065

.;.;.;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.63

M_CAP

Benign

0.050

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.34

.;.;.;N

MutationTaster

Benign

0.93

D;D;D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.17

T;T;T;T

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.069, 0.041

.;B;.;B

Vest4

0.34

MutPred

0.23

.;.;.;Loss of glycosylation at P942 (P = 0.0175);

MVP

0.70

MPC

0.88

ClinPred

0.40

GERP RS

3.6

Varity_R

0.095

gMVP

0.35

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