chr6-29603599-C-T

Position:

• chr6-29603599-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001470.4(GABBR1):​c.2830G>A​(p.Glu944Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GABBR1 NM_001470.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.70

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]

ACMG classification

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=0.2404857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR1	NM_001470.4	c.2830G>A	p.Glu944Lys	missense_variant	23/23	ENST00000377034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR1	ENST00000377034.9	c.2830G>A	p.Glu944Lys	missense_variant	23/23	1	NM_001470.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1435526 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 712310

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	.;.;.;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.093
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.0	.;.;.;N
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.69	N;N;N;N
REVEL	Benign	0.27
Sift	Benign	0.19	T;T;T;T
Sift4G	Benign	0.38	T;T;T;T
Polyphen		0.53, 0.39	.;P;.;B
Vest4		0.36
MutPred		0.29		.;.;.;Gain of methylation at E944 (P = 0.0037);
MVP		0.70
MPC		2.1
ClinPred		0.71	D
GERP RS		3.6
Varity_R		0.11
gMVP		0.27

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

Other links and lift over

dbSNP: rs1243106351; hg19: chr6-29571376;