Variant 5-170811963-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014211.3(GABRP):c.1028C>T(p.Thr343Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000395 in 1,613,212 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 5 hom. )

Consequence

GABRP
NM_014211.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.34

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0074896812).

BP6

Variant 5-170811963-C-T is Benign according to our data. Variant chr5-170811963-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 725278.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GABRP	NM_014211.3 linkuse as main transcript	c.1028C>T	p.Thr343Ile	missense_variant	10/10	ENST00000265294.9	NP_055026.1
GABRP	XM_024446012.2 linkuse as main transcript	c.1028C>T	p.Thr343Ile	missense_variant	10/10		XP_024301780.1
GABRP	XM_005265872.2 linkuse as main transcript	c.791C>T	p.Thr264Ile	missense_variant	8/8		XP_005265929.1
GABRP	NM_001291985.2 linkuse as main transcript	c.840C>T	p.Asn280=	synonymous_variant	9/9		NP_001278914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GABRP	ENST00000265294.9 linkuse as main transcript	c.1028C>T	p.Thr343Ile	missense_variant	10/10	1	NM_014211.3	ENSP00000265294	P1
GABRP	ENST00000518525.5 linkuse as main transcript	c.1028C>T	p.Thr343Ile	missense_variant	11/11	5		ENSP00000430100	P1
GABRP	ENST00000519385.5 linkuse as main transcript	c.840C>T	p.Asn280=	synonymous_variant	9/9	2		ENSP00000430727

Frequencies

GnomAD3 genomes

AF:

0.00200

AC:

305

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00722

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000526

AC:

132

AN:

250774

Hom.:

AF XY:

0.000362

AC XY:

AN XY:

135522

show subpopulations

Gnomad AFR exome

AF:

0.00714

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000227

AC:

332

AN:

1460946

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

143

AN XY:

726668

show subpopulations

Gnomad4 AFR exome

AF:

0.00817

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.00201

AC:

306

AN:

152266

Hom.:

Cov.:

AF XY:

0.00193

AC XY:

144

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00722

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.000399

Hom.:

Bravo

AF:

0.00239

ESP6500AA

AF:

0.00817

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000535

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.069

T;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.32

.;T

M_CAP

Benign

0.050

MetaRNN

Benign

0.0075

T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

-0.55

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.35

N;N

REVEL

Benign

0.20

Sift

Benign

0.20

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.0020

B;B

Vest4

0.076

MVP

0.80

MPC

0.13

ClinPred

0.0062

GERP RS

3.9

Varity_R

0.058

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over