6-89185249-G-A

Variant names:

• chr6-89185249-G-A
• rs407206
• NM_002042.5:c.796+61C>T

Variant summary

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

The NM_002042.5(GABRR1):​c.796+61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,599,704 control chromosomes in the GnomAD database, including 76,982 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 0.25 (5425 hom., cov: 30)
  • Exomes 𝑓: 0.31 (71557 hom.)
• Consequence: GABRR1 NM_002042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR1	NM_002042.5	MANE Select	c.796+61C>T		intron	N/A	NP_002033.2
	GABRR1	NM_001256703.1		c.745+61C>T		intron	N/A	NP_001243632.1
	GABRR1	NM_001256704.1		c.535+61C>T		intron	N/A	NP_001243633.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR1	ENST00000454853.7	TSL:1 MANE Select	c.796+61C>T		intron	N/A	ENSP00000412673.2
	GABRR1	ENST00000435811.5	TSL:2	c.745+61C>T		intron	N/A	ENSP00000394687.1
	GABRR1	ENST00000369451.7	TSL:5	c.535+61C>T		intron	N/A	ENSP00000358463.3

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37946 AN: 151710 Hom.: 5428 Cov.: 30

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.273

GnomAD4 exome AF: 0.308 AC: 446092 AN: 1447876 Hom.: 71557 AF XY: 0.308 AC XY: 222041 AN XY: 721088

African (AFR) AF: 0.114 AC: 3786 AN: 33184

American (AMR) AF: 0.167 AC: 7452 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 8836 AN: 25892

East Asian (EAS) AF: 0.149 AC: 5905 AN: 39622

South Asian (SAS) AF: 0.246 AC: 21093 AN: 85762

European-Finnish (FIN) AF: 0.321 AC: 17086 AN: 53160

Middle Eastern (MID) AF: 0.360 AC: 2009 AN: 5576

European-Non Finnish (NFE) AF: 0.330 AC: 362830 AN: 1100152

Other (OTH) AF: 0.285 AC: 17095 AN: 59928

GnomAD4 genome AF: 0.250 AC: 37948 AN: 151828 Hom.: 5425 Cov.: 30 AF XY: 0.248 AC XY: 18411 AN XY: 74180

African (AFR) AF: 0.123 AC: 5078 AN: 41450

American (AMR) AF: 0.206 AC: 3135 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3466

East Asian (EAS) AF: 0.122 AC: 630 AN: 5146

South Asian (SAS) AF: 0.236 AC: 1132 AN: 4800

European-Finnish (FIN) AF: 0.313 AC: 3289 AN: 10502

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22606 AN: 67916

Other (OTH) AF: 0.270 AC: 569 AN: 2108

Alfa AF: 0.307 Hom.: 12726

Bravo AF: 0.236

Asia WGS AF: 0.164 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.31
PhyloP100		0.056
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: rs407206; hg19: chr6-89894968; COSMIC: COSV65619032;