6-29603768-A-G

Variant names:

• chr6-29603768-A-G
• rs2076483
• NM_001470.4:c.2713-52T>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.2713-52T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,329,444 control chromosomes in the GnomAD database, including 11,242 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 0.12 (1410 hom., cov: 31)
  • Exomes 𝑓: 0.12 (9832 hom.)
• Consequence: GABBR1 NM_001470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 23 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001470.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABBR1	NM_001470.4	MANE Select	c.2713-52T>C		intron	N/A	NP_001461.1
	GABBR1	NM_021904.4		c.2527-52T>C		intron	N/A	NP_068704.2
	GABBR1	NM_021903.3		c.2362-52T>C		intron	N/A	NP_068703.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABBR1	ENST00000377034.9	TSL:1 MANE Select	c.2713-52T>C		intron	N/A	ENSP00000366233.4
	GABBR1	ENST00000377012.9	TSL:1	c.2362-52T>C		intron	N/A	ENSP00000366211.4
	GABBR1	ENST00000476670.3	TSL:4	c.2728-52T>C		intron	N/A	ENSP00000417332.2

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18956 AN: 151618 Hom.: 1410 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.0624

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.155

GnomAD2 exomes AF: 0.133 AC: 12794 AN: 96082 AF XY: 0.138

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.158

Gnomad EAS exome AF: 0.229

Gnomad FIN exome AF: 0.0455

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.119 AC: 140486 AN: 1177708 Hom.: 9832 Cov.: 18 AF XY: 0.123 AC XY: 70014 AN XY: 571070

African (AFR) AF: 0.0958 AC: 2566 AN: 26790

American (AMR) AF: 0.131 AC: 2242 AN: 17058

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 2791 AN: 16984

East Asian (EAS) AF: 0.217 AC: 7413 AN: 34146

South Asian (SAS) AF: 0.265 AC: 11821 AN: 44636

European-Finnish (FIN) AF: 0.0578 AC: 2138 AN: 37014

Middle Eastern (MID) AF: 0.227 AC: 1102 AN: 4862

European-Non Finnish (NFE) AF: 0.109 AC: 103603 AN: 947252

Other (OTH) AF: 0.139 AC: 6810 AN: 48966

GnomAD4 genome AF: 0.125 AC: 18965 AN: 151736 Hom.: 1410 Cov.: 31 AF XY: 0.128 AC XY: 9487 AN XY: 74180

African (AFR) AF: 0.107 AC: 4440 AN: 41328

American (AMR) AF: 0.120 AC: 1826 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 575 AN: 3468

East Asian (EAS) AF: 0.252 AC: 1290 AN: 5116

South Asian (SAS) AF: 0.297 AC: 1424 AN: 4790

European-Finnish (FIN) AF: 0.0624 AC: 659 AN: 10568

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8261 AN: 67910

Other (OTH) AF: 0.154 AC: 323 AN: 2092

Alfa AF: 0.122 Hom.: 3110

Bravo AF: 0.126

Asia WGS AF: 0.214 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.61
PhyloP100		-1.0
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: rs2076483; hg19: chr6-29571545;