chr6-29614868-C-T

Variant names:

• chr6-29614868-C-T
• rs74294678
• NM_001470.4:c.1324-1383G>A

Variant summary

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

The NM_001470.4(GABBR1):​c.1324-1383G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 147,108 control chromosomes in the GnomAD database, including 32 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 0.014 (32 hom., cov: 32)
• Consequence: GABBR1 NM_001470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371
• Publications: 1 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 (EAS) allele frequency at 95% confidence interval = 0.086 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.1324-1383G>A		intron	N/A	NP_001461.1
	GABBR1	NM_021904.4		c.1138-1383G>A		intron	N/A	NP_068704.2
	GABBR1	NM_021903.3		c.973-1383G>A		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.1324-1383G>A		intron	N/A	ENSP00000366233.4
	GABBR1	ENST00000377012.9	TSL:1	c.973-1383G>A		intron	N/A	ENSP00000366211.4
	GABBR1	ENST00000476670.3	TSL:4	c.1339-1383G>A		intron	N/A	ENSP00000417332.2

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 2007 AN: 147000 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.00442

Gnomad AMR AF: 0.00696

Gnomad ASJ AF: 0.00408

Gnomad EAS AF: 0.0932

Gnomad SAS AF: 0.0601

Gnomad FIN AF: 0.00370

Gnomad MID AF: 0.0201

Gnomad NFE AF: 0.00296

Gnomad OTH AF: 0.0133

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0136 AC: 2006 AN: 147108 Hom.: 32 Cov.: 32 AF XY: 0.0152 AC XY: 1083 AN XY: 71376

African (AFR) AF: 0.0221 AC: 878 AN: 39774

American (AMR) AF: 0.00695 AC: 99 AN: 14238

Ashkenazi Jewish (ASJ) AF: 0.00408 AC: 14 AN: 3434

East Asian (EAS) AF: 0.0930 AC: 462 AN: 4966

South Asian (SAS) AF: 0.0599 AC: 282 AN: 4706

European-Finnish (FIN) AF: 0.00370 AC: 35 AN: 9450

Middle Eastern (MID) AF: 0.0214 AC: 6 AN: 280

European-Non Finnish (NFE) AF: 0.00296 AC: 199 AN: 67300

Other (OTH) AF: 0.0131 AC: 27 AN: 2056

Alfa AF: 0.00724 Hom.: 1

Bravo AF: 0.0140

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.74
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism

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: rs74294678; hg19: chr6-29582645;