rs1139916

chrX-151969707-A-CchrX-151969707-A-GchrX-151969707-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004961.4(GABRE):c.304T>G(p.Ser102Ala) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.64 (16408 hom., 20676 hem., cov: 22)
  • Exomes 𝑓: 0.70 (178081 hom. 253983 hem.)
  • Failed GnomAD Quality Control
• Consequence: GABRE NM_004961.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.11

Genes affected

GABRE (HGNC:4085): (gamma-aminobutyric acid type A receptor subunit epsilon) The product of this gene belongs to the ligand-gated ionic channel (TC 1.A.9) family. It encodes the gamma-aminobutyric acid (GABA) A receptor which is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes an epsilon subunit. It is mapped to chromosome Xq28 in a cluster comprised of genes encoding alpha 3, beta 4 and theta subunits of the same receptor. Alternatively spliced transcript variants have been identified, but only one is thought to encode a protein. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0047327E-4).
• BP6: Variant X-151969707-A-C is Benign according to our data. Variant chrX-151969707-A-C is described in ClinVar as [Benign]. Clinvar id is 1280403.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 16409 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRE	NM_004961.4	c.304T>G	p.Ser102Ala	missense_variant	3/9	ENST00000370328.4
GABRE	XM_024452360.2	c.-36T>G		5_prime_UTR_variant	4/10
GABRE	XM_047441959.1	c.-36T>G		5_prime_UTR_variant	3/9
GABRE	XM_047441960.1	c.-36T>G		5_prime_UTR_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRE	ENST00000370328.4	c.304T>G	p.Ser102Ala	missense_variant	3/9	1	NM_004961.4	P1
GABRE	ENST00000465405.1	n.398T>G		non_coding_transcript_exon_variant	2/2	1
GABRE	ENST00000474932.1	n.30T>G		non_coding_transcript_exon_variant	1/3	5
GABRE	ENST00000441219.5	c.*350T>G		3_prime_UTR_variant, NMD_transcript_variant	4/8	2

Frequencies

GnomAD3 genomes AF: 0.644 AC: 70536 AN: 109473 Hom.: 16409 Cov.: 22 AF XY: 0.650 AC XY: 20649 AN XY: 31775

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.625

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.624

GnomAD3 exomes AF: 0.716 AC: 130407 AN: 182165 Hom.: 29673 AF XY: 0.726 AC XY: 48429 AN XY: 66681

Gnomad AFR exome AF: 0.494

Gnomad AMR exome AF: 0.747

Gnomad ASJ exome AF: 0.610

Gnomad EAS exome AF: 0.868

Gnomad SAS exome AF: 0.818

Gnomad FIN exome AF: 0.801

Gnomad NFE exome AF: 0.685

Gnomad OTH exome AF: 0.715

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.696 AC: 763144 AN: 1096589 Hom.: 178081 Cov.: 33 AF XY: 0.701 AC XY: 253983 AN XY: 362189

Gnomad4 AFR exome AF: 0.487

Gnomad4 AMR exome AF: 0.748

Gnomad4 ASJ exome AF: 0.612

Gnomad4 EAS exome AF: 0.893

Gnomad4 SAS exome AF: 0.817

Gnomad4 FIN exome AF: 0.795

Gnomad4 NFE exome AF: 0.683

Gnomad4 OTH exome AF: 0.685

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.644 AC: 70564 AN: 109531 Hom.: 16408 Cov.: 22 AF XY: 0.649 AC XY: 20676 AN XY: 31843

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.871

Gnomad4 SAS AF: 0.804

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.627

Alfa AF: 0.682 Hom.: 63764

Bravo AF: 0.632

TwinsUK AF: 0.677 AC: 2509

ALSPAC AF: 0.694 AC: 2004

ESP6500AA AF: 0.504 AC: 1933

ESP6500EA AF: 0.670 AC: 4511

ExAC AF: 0.716 AC: 86879

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 14, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	14
Dann	Benign	0.96
DEOGEN2	Benign	0.061	T
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.00010	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.21
Sift	Uncertain	0.017	D
Sift4G	Benign	0.16	T
Polyphen		0.78	P
Vest4		0.032
MPC		0.082
ClinPred		0.024	T
GERP RS		2.7
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1
Varity_R		0.17
gMVP		0.27

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: rs1139916; hg19: chrX-151138179; COSMIC: COSV64820319; COSMIC: COSV64820319;