rs55941866

Variant names:

• chr6-29603800-G-A
• rs55941866
• NM_001470.4:c.2713-84C>T

Variant summary

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

The NM_001470.4(GABBR1):​c.2713-84C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 1,066,380 control chromosomes in the GnomAD database, including 968 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 0.036 (198 hom., cov: 31)
  • Exomes 𝑓: 0.030 (770 hom.)
• Consequence: GABBR1 NM_001470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 0 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=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0908 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.2713-84C>T		intron	N/A	NP_001461.1	A0A1U9X7R0
	GABBR1	NM_021904.4		c.2527-84C>T		intron	N/A	NP_068704.2	Q9UBS5-3
	GABBR1	NM_021903.3		c.2362-84C>T		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.2713-84C>T		intron	N/A	ENSP00000366233.4	Q9UBS5-1
	GABBR1	ENST00000377012.9	TSL:1	c.2362-84C>T		intron	N/A	ENSP00000366211.4	Q9UBS5-2
	GABBR1	ENST00000476670.3	TSL:4	c.2728-84C>T		intron	N/A	ENSP00000417332.2	C9J342

Frequencies

GnomAD3 genomes AF: 0.0362 AC: 5499 AN: 152036 Hom.: 199 Cov.: 31

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0935

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0476

Gnomad SAS AF: 0.0966

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0281

Gnomad OTH AF: 0.0374

GnomAD4 exome AF: 0.0299 AC: 27347 AN: 914226 Hom.: 770 AF XY: 0.0320 AC XY: 14278 AN XY: 446460

African (AFR) AF: 0.0148 AC: 316 AN: 21382

American (AMR) AF: 0.0979 AC: 1292 AN: 13196

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 1951 AN: 15022

East Asian (EAS) AF: 0.0456 AC: 1415 AN: 31016

South Asian (SAS) AF: 0.107 AC: 3671 AN: 34288

European-Finnish (FIN) AF: 0.0234 AC: 691 AN: 29470

Middle Eastern (MID) AF: 0.0732 AC: 320 AN: 4374

European-Non Finnish (NFE) AF: 0.0221 AC: 16038 AN: 725210

Other (OTH) AF: 0.0411 AC: 1653 AN: 40268

GnomAD4 genome AF: 0.0362 AC: 5504 AN: 152154 Hom.: 198 Cov.: 31 AF XY: 0.0379 AC XY: 2817 AN XY: 74390

African (AFR) AF: 0.0168 AC: 696 AN: 41502

American (AMR) AF: 0.0934 AC: 1429 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3468

East Asian (EAS) AF: 0.0477 AC: 246 AN: 5160

South Asian (SAS) AF: 0.0981 AC: 472 AN: 4812

European-Finnish (FIN) AF: 0.0191 AC: 203 AN: 10610

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0281 AC: 1910 AN: 67990

Other (OTH) AF: 0.0370 AC: 78 AN: 2108

Alfa AF: 0.0299 Hom.: 10

Bravo AF: 0.0399

Asia WGS AF: 0.0710 AC: 249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.1
DANN	Benign	0.82
PhyloP100		0.049
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs55941866; hg19: chr6-29571577;