rs404943

Variant names:

• chr6-89181863-T-C
• rs404943
• NM_002042.5:c.949+42A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-89181863-T-C
• chr6-89181863-T-G

Variant summary

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

The NM_002042.5(GABRR1):​c.949+42A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,538,000 control chromosomes in the GnomAD database, including 75,328 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 0.31 (7591 hom., cov: 32)
  • Exomes 𝑓: 0.31 (67737 hom.)
• Consequence: GABRR1 NM_002042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.836
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR1	NM_002042.5	c.949+42A>G		intron_variant	Intron 8 of 9	ENST00000454853.7	NP_002033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000454853.7	c.949+42A>G		intron_variant	Intron 8 of 9	1	NM_002042.5	ENSP00000412673.2
GABRR1	ENST00000435811.5	c.898+42A>G		intron_variant	Intron 7 of 8	2		ENSP00000394687.1
GABRR1	ENST00000369451.7	c.688+42A>G		intron_variant	Intron 10 of 11	5		ENSP00000358463.3
GABRR1	ENST00000457434.1	n.*910+42A>G		intron_variant	Intron 9 of 10	5		ENSP00000410130.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46998 AN: 151944 Hom.: 7600 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.284

GnomAD2 exomes AF: 0.334 AC: 74557 AN: 222942 AF XY: 0.330

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.370

Gnomad ASJ exome AF: 0.250

Gnomad EAS exome AF: 0.639

Gnomad FIN exome AF: 0.377

Gnomad NFE exome AF: 0.280

Gnomad OTH exome AF: 0.305

GnomAD4 exome AF: 0.305 AC: 423057 AN: 1385938 Hom.: 67737 Cov.: 24 AF XY: 0.305 AC XY: 209194 AN XY: 686476

African (AFR) AF: 0.277 AC: 8614 AN: 31126

American (AMR) AF: 0.365 AC: 13350 AN: 36620

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 5777 AN: 23204

East Asian (EAS) AF: 0.622 AC: 24092 AN: 38764

South Asian (SAS) AF: 0.346 AC: 25822 AN: 74560

European-Finnish (FIN) AF: 0.375 AC: 19154 AN: 51068

Middle Eastern (MID) AF: 0.225 AC: 1230 AN: 5468

European-Non Finnish (NFE) AF: 0.288 AC: 307133 AN: 1068054

Other (OTH) AF: 0.313 AC: 17885 AN: 57074

GnomAD4 genome AF: 0.309 AC: 47000 AN: 152062 Hom.: 7591 Cov.: 32 AF XY: 0.319 AC XY: 23737 AN XY: 74322

African (AFR) AF: 0.282 AC: 11687 AN: 41456

American (AMR) AF: 0.343 AC: 5237 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 892 AN: 3472

East Asian (EAS) AF: 0.633 AC: 3266 AN: 5160

South Asian (SAS) AF: 0.362 AC: 1743 AN: 4820

European-Finnish (FIN) AF: 0.377 AC: 3988 AN: 10586

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19195 AN: 67988

Other (OTH) AF: 0.280 AC: 588 AN: 2098

Alfa AF: 0.283 Hom.: 2279

Bravo AF: 0.306

Asia WGS AF: 0.434 AC: 1510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.44
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs404943; hg19: chr6-89891582; COSMIC: COSV65619025;