rs29225

Variant names:

• chr6-29613264-A-C
• rs29225
• NM_001470.4:c.1545T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-29613264-A-C
• chr6-29613264-A-G
• chr6-29613264-A-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001470.4(GABBR1):​c.1545T>G​(p.Ser515Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: GABBR1 NM_001470.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 19 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=1 with no splicing effect.

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.1545T>G	p.Ser515Ser	synonymous	Exon 12 of 23	NP_001461.1	A0A1U9X7R0
	GABBR1	NM_021904.4		c.1359T>G	p.Ser453Ser	synonymous	Exon 11 of 22	NP_068704.2	Q9UBS5-3
	GABBR1	NM_021903.3		c.1194T>G	p.Ser398Ser	synonymous	Exon 7 of 18	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.1545T>G	p.Ser515Ser	synonymous	Exon 12 of 23	ENSP00000366233.4	Q9UBS5-1
	GABBR1	ENST00000377012.9	TSL:1	c.1194T>G	p.Ser398Ser	synonymous	Exon 7 of 18	ENSP00000366211.4	Q9UBS5-2
	GABBR1	ENST00000476670.3	TSL:4	c.1560T>G	p.Ser520Ser	synonymous	Exon 12 of 23	ENSP00000417332.2	C9J342

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2321

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.5
DANN	Benign	0.70
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs29225; hg19: chr6-29581041;