Variant rs1063310 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014211.3(GABRP):c.1173C>A(p.Phe391Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,613,838 control chromosomes in the GnomAD database, including 45,146 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.25 ( 4821 hom., cov: 33)

Exomes 𝑓: 0.23 ( 40325 hom. )

Consequence

GABRP
NM_014211.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.715

Variant links:

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]

GABRP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016617179).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GABRP	NM_014211.3 linkuse as main transcript	c.1173C>A	p.Phe391Leu	missense_variant	10/10	ENST00000265294.9
GABRP	XM_024446012.2 linkuse as main transcript	c.1173C>A	p.Phe391Leu	missense_variant	10/10
GABRP	XM_005265872.2 linkuse as main transcript	c.936C>A	p.Phe312Leu	missense_variant	8/8
GABRP	NM_001291985.2 linkuse as main transcript	c.*115C>A		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GABRP	ENST00000265294.9 linkuse as main transcript	c.1173C>A	p.Phe391Leu	missense_variant	10/10	1	NM_014211.3	P1
GABRP	ENST00000518525.5 linkuse as main transcript	c.1173C>A	p.Phe391Leu	missense_variant	11/11	5		P1
GABRP	ENST00000519385.5 linkuse as main transcript	c.*115C>A		3_prime_UTR_variant	9/9	2

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37294

AN:

151954

Hom.:

4810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.292

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.139

Gnomad FIN

AF:

0.285

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.236

Gnomad OTH

AF:

0.233

GnomAD3 exomes

AF:

0.219

AC:

54992

AN:

251344

Hom.:

6546

AF XY:

0.220

AC XY:

29845

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.293

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.280

Gnomad SAS exome

AF:

0.139

Gnomad FIN exome

AF:

0.277

Gnomad NFE exome

AF:

0.238

Gnomad OTH exome

AF:

0.220

GnomAD4 exome

AF:

0.232

AC:

338662

AN:

1461766

Hom.:

40325

Cov.:

AF XY:

0.229

AC XY:

166881

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.289

Gnomad4 AMR exome

AF:

0.122

Gnomad4 ASJ exome

AF:

0.252

Gnomad4 EAS exome

AF:

0.277

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.272

Gnomad4 NFE exome

AF:

0.237

Gnomad4 OTH exome

AF:

0.227

GnomAD4 genome

AF:

0.245

AC:

37333

AN:

152072

Hom.:

4821

Cov.:

AF XY:

0.245

AC XY:

18235

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.292

Gnomad4 AMR

AF:

0.171

Gnomad4 ASJ

AF:

0.248

Gnomad4 EAS

AF:

0.277

Gnomad4 SAS

AF:

0.138

Gnomad4 FIN

AF:

0.285

Gnomad4 NFE

AF:

0.237

Gnomad4 OTH

AF:

0.231

Alfa

AF:

0.241

Hom.:

8880

Bravo

AF:

0.244

TwinsUK

AF:

0.226

AC:

837

ALSPAC

AF:

0.230

AC:

887

ESP6500AA

AF:

0.304

AC:

1338

ESP6500EA

AF:

0.244

AC:

2099

ExAC

AF:

0.222

AC:

26949

Asia WGS

AF:

0.188

AC:

655

AN:

3478

EpiCase

AF:

0.238

EpiControl

AF:

0.240

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.044

T;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.51

.;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;L

MutationTaster

Benign

0.61

P;P;P

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.11

N;N

REVEL

Benign

0.12

Sift

Benign

0.69

T;T

Sift4G

Benign

0.69

T;T

Polyphen

0.042

B;B

Vest4

0.080

MutPred

0.13

Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);

MPC

0.14

ClinPred

0.0091

GERP RS

2.9

Varity_R

0.051

gMVP

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over