rs72831507

Variant names:

• chr6-29617966-G-T
• rs72831507
• NM_001470.4:c.1323+3135C>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.1323+3135C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.055 in 152,212 control chromosomes in the GnomAD database, including 336 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 0.055 (336 hom., cov: 32)
• Consequence: GABBR1 NM_001470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.271
• 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=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR1	NM_001470.4	c.1323+3135C>A		intron_variant	Intron 11 of 22	ENST00000377034.9	NP_001461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR1	ENST00000377034.9	c.1323+3135C>A		intron_variant	Intron 11 of 22	1	NM_001470.4	ENSP00000366233.4

Frequencies

GnomAD3 genomes AF: 0.0550 AC: 8360 AN: 152094 Hom.: 334 Cov.: 32

Gnomad AFR AF: 0.0426

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0507

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0340

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0557

Gnomad OTH AF: 0.0646

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

GnomAD4 genome AF: 0.0550 AC: 8366 AN: 152212 Hom.: 336 Cov.: 32 AF XY: 0.0573 AC XY: 4263 AN XY: 74412

African (AFR) AF: 0.0426 AC: 1767 AN: 41524

American (AMR) AF: 0.0507 AC: 775 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0357 AC: 124 AN: 3472

East Asian (EAS) AF: 0.123 AC: 638 AN: 5182

South Asian (SAS) AF: 0.139 AC: 669 AN: 4828

European-Finnish (FIN) AF: 0.0340 AC: 360 AN: 10596

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0557 AC: 3790 AN: 67994

Other (OTH) AF: 0.0639 AC: 135 AN: 2112

Alfa AF: 0.0537 Hom.: 25

Bravo AF: 0.0543

Asia WGS AF: 0.0920 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	10
DANN	Benign	0.77
PhyloP100		0.27
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: rs72831507; hg19: chr6-29585743;