NM_002042.5:c.123-5G>C

Variant names:

• chr6-89203490-C-G
• rs4590242
• NM_002042.5:c.123-5G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002042.5(GABRR1):​c.123-5G>C variant causes a splice region, intron 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GABRR1 NM_002042.5 splice_region, intron
• Scores: Splicing: ADA: 0.00002205
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 13 publications found

Genes affected

GABRR1 (HGNC:4090): (gamma-aminobutyric acid type A receptor subunit rho1) GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA receptors, which are ligand-gated chloride channels. GABRR1 is a member of the rho subunit family. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002042.5. 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
	GABRR1	NM_002042.5	MANE Select	c.123-5G>C		splice_region intron	N/A	NP_002033.2	P24046-1
	GABRR1	NM_001256703.1		c.123-2225G>C		intron	N/A	NP_001243632.1	P24046-2
	GABRR1	NM_001256704.1		c.-142-2G>C		splice_acceptor intron	N/A	NP_001243633.1	P24046-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR1	ENST00000454853.7	TSL:1 MANE Select	c.123-5G>C		splice_region intron	N/A	ENSP00000412673.2	P24046-1
	GABRR1	ENST00000435811.5	TSL:2	c.123-2225G>C		intron	N/A	ENSP00000394687.1	P24046-2
	GABRR1	ENST00000369451.7	TSL:5	c.-139-5G>C		splice_region intron	N/A	ENSP00000358463.3	P24046-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.0
DANN	Benign	0.58
PhyloP100		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000022
dbscSNV1_RF	Benign	0.0
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: rs4590242; hg19: chr6-89913209;