6-29621889-C-G

Variant names:

• chr6-29621889-C-G
• rs29220
• NM_001470.4:c.1066-72G>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.1066-72G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,483,088 control chromosomes in the GnomAD database, including 60,706 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 0.31 (7667 hom., cov: 32)
  • Exomes 𝑓: 0.28 (53039 hom.)
• Consequence: GABBR1 NM_001470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 20 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABBR1	NM_001470.4	MANE Select	c.1066-72G>C		intron	N/A	NP_001461.1	A0A1U9X7R0
	GABBR1	NM_021904.4		c.880-72G>C		intron	N/A	NP_068704.2	Q9UBS5-3
	GABBR1	NM_021903.3		c.715-72G>C		intron	N/A	NP_068703.1	Q5SUJ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABBR1	ENST00000377034.9	TSL:1 MANE Select	c.1066-72G>C		intron	N/A	ENSP00000366233.4	Q9UBS5-1
	GABBR1	ENST00000377012.9	TSL:1	c.715-72G>C		intron	N/A	ENSP00000366211.4	Q9UBS5-2
	GABBR1	ENST00000476670.3	TSL:4	c.1081-72G>C		intron	N/A	ENSP00000417332.2	C9J342

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47338 AN: 151980 Hom.: 7650 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.316

GnomAD4 exome AF: 0.276 AC: 367437 AN: 1330990 Hom.: 53039 Cov.: 19 AF XY: 0.278 AC XY: 185804 AN XY: 668912

African (AFR) AF: 0.346 AC: 10564 AN: 30552

American (AMR) AF: 0.282 AC: 12188 AN: 43178

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 4904 AN: 25096

East Asian (EAS) AF: 0.389 AC: 15107 AN: 38884

South Asian (SAS) AF: 0.382 AC: 31683 AN: 82996

European-Finnish (FIN) AF: 0.418 AC: 22070 AN: 52746

Middle Eastern (MID) AF: 0.264 AC: 1425 AN: 5400

European-Non Finnish (NFE) AF: 0.255 AC: 253954 AN: 996386

Other (OTH) AF: 0.279 AC: 15542 AN: 55752

GnomAD4 genome AF: 0.312 AC: 47391 AN: 152098 Hom.: 7667 Cov.: 32 AF XY: 0.320 AC XY: 23820 AN XY: 74324

African (AFR) AF: 0.346 AC: 14368 AN: 41490

American (AMR) AF: 0.303 AC: 4634 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 660 AN: 3470

East Asian (EAS) AF: 0.415 AC: 2145 AN: 5174

South Asian (SAS) AF: 0.386 AC: 1861 AN: 4822

European-Finnish (FIN) AF: 0.430 AC: 4542 AN: 10552

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18291 AN: 67980

Other (OTH) AF: 0.321 AC: 678 AN: 2110

Alfa AF: 0.267 Hom.: 3146

Bravo AF: 0.302

Asia WGS AF: 0.460 AC: 1600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.63
DANN	Benign	0.63
PhyloP100		-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: rs29220; hg19: chr6-29589666;