rs11134654

Positions:

• chr5-170813419-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014211.3(GABRP):​c.*1161A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,280 control chromosomes in the GnomAD database, including 50,908 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 0.82 (50881 hom., cov: 33)
  • Exomes 𝑓: 0.83 (27 hom.)
• Consequence: GABRP NM_014211.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

Genes affected

GABRP (HGNC:4089): (gamma-aminobutyric acid type A receptor subunit pi) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. The subunit encoded by this gene is expressed in several non-neuronal tissues including the uterus and ovaries. This subunit can assemble with known GABA A receptor subunits, and the presence of this subunit alters the sensitivity of recombinant receptors to modulatory agents such as pregnanolone. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRP	NM_014211.3	c.*1161A>C		3_prime_UTR_variant	10/10	ENST00000265294.9	NP_055026.1
GABRP	NM_001291985.2	c.*1426A>C		3_prime_UTR_variant	9/9		NP_001278914.1
GABRP	XM_005265872.2	c.*1161A>C		3_prime_UTR_variant	8/8		XP_005265929.1
GABRP	XM_024446012.2	c.*1161A>C		3_prime_UTR_variant	10/10		XP_024301780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRP	ENST00000265294.9	c.*1161A>C		3_prime_UTR_variant	10/10	1	NM_014211.3	ENSP00000265294	P1
GABRP	ENST00000518525.5	c.*1161A>C		3_prime_UTR_variant	11/11	5		ENSP00000430100	P1

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124046 AN: 152084 Hom.: 50834 Cov.: 33

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.866

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.820

GnomAD4 exome AF: 0.833 AC: 65 AN: 78 Hom.: 27 Cov.: 0 AF XY: 0.879 AC XY: 51 AN XY: 58

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.827

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.816 AC: 124146 AN: 152202 Hom.: 50881 Cov.: 33 AF XY: 0.820 AC XY: 60982 AN XY: 74410

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.842

Gnomad4 ASJ AF: 0.866

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.946

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.818

Gnomad4 OTH AF: 0.821

Alfa AF: 0.817 Hom.: 46516

Bravo AF: 0.816

Asia WGS AF: 0.955 AC: 3321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.16
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs11134654; hg19: chr5-170240423;