chr6-29613234-T-G

Variant names:

• chr6-29613234-T-G
• rs29226
• NM_001470.4:c.1566+9A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001470.4(GABBR1):​c.1566+9A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0985 in 1,607,742 control chromosomes in the GnomAD database, including 8,559 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 0.098 (871 hom., cov: 32)
  • Exomes 𝑓: 0.099 (7688 hom.)
• Consequence: GABBR1 NM_001470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.794
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with language delay and variable cognitive abnormalities

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR1	NM_001470.4	c.1566+9A>C		intron_variant	Intron 12 of 22	ENST00000377034.9	NP_001461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR1	ENST00000377034.9	c.1566+9A>C		intron_variant	Intron 12 of 22	1	NM_001470.4	ENSP00000366233.4

Frequencies

GnomAD3 genomes AF: 0.0983 AC: 14958 AN: 152140 Hom.: 868 Cov.: 32

Gnomad AFR AF: 0.0897

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.120

GnomAD2 exomes AF: 0.0992 AC: 24381 AN: 245744 AF XY: 0.103

Gnomad AFR exome AF: 0.0972

Gnomad AMR exome AF: 0.0712

Gnomad ASJ exome AF: 0.0867

Gnomad EAS exome AF: 0.148

Gnomad FIN exome AF: 0.0467

Gnomad NFE exome AF: 0.101

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.0985 AC: 143370 AN: 1455484 Hom.: 7688 Cov.: 32 AF XY: 0.100 AC XY: 72699 AN XY: 723932

African (AFR) AF: 0.0916 AC: 3059 AN: 33380

American (AMR) AF: 0.0752 AC: 3361 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.0902 AC: 2351 AN: 26074

East Asian (EAS) AF: 0.0843 AC: 3345 AN: 39658

South Asian (SAS) AF: 0.142 AC: 12252 AN: 86038

European-Finnish (FIN) AF: 0.0501 AC: 2618 AN: 52294

Middle Eastern (MID) AF: 0.164 AC: 941 AN: 5746

European-Non Finnish (NFE) AF: 0.0984 AC: 108941 AN: 1107426

Other (OTH) AF: 0.108 AC: 6502 AN: 60198

GnomAD4 genome AF: 0.0983 AC: 14965 AN: 152258 Hom.: 871 Cov.: 32 AF XY: 0.0992 AC XY: 7389 AN XY: 74458

African (AFR) AF: 0.0897 AC: 3726 AN: 41554

American (AMR) AF: 0.0998 AC: 1526 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0862 AC: 299 AN: 3470

East Asian (EAS) AF: 0.129 AC: 667 AN: 5184

South Asian (SAS) AF: 0.165 AC: 797 AN: 4816

European-Finnish (FIN) AF: 0.0439 AC: 466 AN: 10616

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7050 AN: 68004

Other (OTH) AF: 0.119 AC: 251 AN: 2114

Alfa AF: 0.0994 Hom.: 1272

Bravo AF: 0.103

Asia WGS AF: 0.122 AC: 423 AN: 3478

EpiCase AF: 0.116

EpiControl AF: 0.110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.53
PhyloP100		-0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs29226; hg19: chr6-29581011; COSMIC: COSV63543620; COSMIC: COSV63543620;