rs1139916

Variant names:

• chrX-151969707-A-C
• rs1139916
• NM_004961.4:c.304T>G

Your query was ambiguous. Multiple possible variants found:

• chrX-151969707-A-C
• chrX-151969707-A-G
• chrX-151969707-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.11
• Publications: 38 publications found

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

Our verdict: Benign. The variant received -12 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_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRE	NM_004961.4	c.304T>G	p.Ser102Ala	missense_variant	Exon 3 of 9	ENST00000370328.4	NP_004952.2
GABRE	XM_024452360.2	c.-36T>G		5_prime_UTR_variant	Exon 4 of 10		XP_024308128.1
GABRE	XM_047441959.1	c.-36T>G		5_prime_UTR_variant	Exon 3 of 9		XP_047297915.1
GABRE	XM_047441960.1	c.-36T>G		5_prime_UTR_variant	Exon 2 of 9		XP_047297916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRE	ENST00000370328.4	c.304T>G	p.Ser102Ala	missense_variant	Exon 3 of 9	1	NM_004961.4	ENSP00000359353.3

Frequencies

GnomAD3 genomes AF: 0.644 AC: 70536 AN: 109473 Hom.: 16409 Cov.: 22

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

GnomAD2 exomes AF: 0.716 AC: 130407 AN: 182165 AF XY: 0.726

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 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

African (AFR) AF: 0.487 AC: 12853 AN: 26369

American (AMR) AF: 0.748 AC: 26264 AN: 35128

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 11849 AN: 19361

East Asian (EAS) AF: 0.893 AC: 26951 AN: 30175

South Asian (SAS) AF: 0.817 AC: 43998 AN: 53847

European-Finnish (FIN) AF: 0.795 AC: 32201 AN: 40498

Middle Eastern (MID) AF: 0.709 AC: 2919 AN: 4115

European-Non Finnish (NFE) AF: 0.683 AC: 574572 AN: 841055

Other (OTH) AF: 0.685 AC: 31537 AN: 46041

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

African (AFR) AF: 0.497 AC: 14913 AN: 30026

American (AMR) AF: 0.684 AC: 7047 AN: 10308

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 1571 AN: 2625

East Asian (EAS) AF: 0.871 AC: 2995 AN: 3437

South Asian (SAS) AF: 0.804 AC: 1981 AN: 2465

European-Finnish (FIN) AF: 0.809 AC: 4623 AN: 5713

Middle Eastern (MID) AF: 0.637 AC: 135 AN: 212

European-Non Finnish (NFE) AF: 0.684 AC: 35942 AN: 52576

Other (OTH) AF: 0.627 AC: 938 AN: 1496

Alfa AF: 0.671 Hom.: 68580

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 14, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
PhyloP100		4.1
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
Mutation Taster		=296/4	polymorphism (auto)

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

Other links and lift over

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