NM_000171.4:c.913-262A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000171.4(GLRA1):​c.913-262A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,034 control chromosomes in the GnomAD database, including 17,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.47 ( 17281 hom., cov: 32)

Consequence

GLRA1
NM_000171.4 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.839

Publications

2 publications found
Variant links:
Genes affected
GLRA1 (HGNC:4326): (glycine receptor alpha 1) The protein encoded by this gene is a subunit of a pentameric inhibitory glycine receptor, which mediates postsynaptic inhibition in the central nervous system. Defects in this gene are a cause of startle disease (STHE), also known as hereditary hyperekplexia or congenital stiff-person syndrome. Multiple transcript variants encoding different isoforms have been found. [provided by RefSeq, Dec 2015]
GLRA1 Gene-Disease associations (from GenCC):
  • hyperekplexia 1
    Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
  • hereditary hyperekplexia
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BP6
Variant 5-151829329-T-C is Benign according to our data. Variant chr5-151829329-T-C is described in ClinVar as [Benign]. Clinvar id is 1283942.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GLRA1NM_000171.4 linkc.913-262A>G intron_variant Intron 7 of 8 ENST00000274576.9 NP_000162.2 P23415-2
GLRA1NM_001146040.2 linkc.913-262A>G intron_variant Intron 7 of 8 NP_001139512.1 P23415-1
GLRA1NM_001292000.2 linkc.664-262A>G intron_variant Intron 6 of 7 NP_001278929.1 Q14C71
GLRA1XM_047417105.1 linkc.961-262A>G intron_variant Intron 7 of 8 XP_047273061.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GLRA1ENST00000274576.9 linkc.913-262A>G intron_variant Intron 7 of 8 1 NM_000171.4 ENSP00000274576.5 P23415-2
GLRA1ENST00000455880.2 linkc.913-262A>G intron_variant Intron 7 of 8 1 ENSP00000411593.2 P23415-1
GLRA1ENST00000462581.6 linkn.*671-262A>G intron_variant Intron 6 of 7 1 ENSP00000430595.1 E5RJ70

Frequencies

GnomAD3 genomes
AF:
0.466
AC:
70755
AN:
151916
Hom.:
17246
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.621
Gnomad AMI
AF:
0.294
Gnomad AMR
AF:
0.390
Gnomad ASJ
AF:
0.365
Gnomad EAS
AF:
0.320
Gnomad SAS
AF:
0.467
Gnomad FIN
AF:
0.419
Gnomad MID
AF:
0.383
Gnomad NFE
AF:
0.415
Gnomad OTH
AF:
0.441
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.466
AC:
70837
AN:
152034
Hom.:
17281
Cov.:
32
AF XY:
0.463
AC XY:
34408
AN XY:
74298
show subpopulations
African (AFR)
AF:
0.621
AC:
25746
AN:
41464
American (AMR)
AF:
0.390
AC:
5954
AN:
15266
Ashkenazi Jewish (ASJ)
AF:
0.365
AC:
1268
AN:
3470
East Asian (EAS)
AF:
0.320
AC:
1654
AN:
5174
South Asian (SAS)
AF:
0.465
AC:
2244
AN:
4822
European-Finnish (FIN)
AF:
0.419
AC:
4424
AN:
10554
Middle Eastern (MID)
AF:
0.367
AC:
108
AN:
294
European-Non Finnish (NFE)
AF:
0.415
AC:
28236
AN:
67974
Other (OTH)
AF:
0.444
AC:
936
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1903
3807
5710
7614
9517
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
638
1276
1914
2552
3190
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.446
Hom.:
5185
Bravo
AF:
0.467
Asia WGS
AF:
0.447
AC:
1551
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jul 05, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
1.7
DANN
Benign
0.78
PhyloP100
-0.84
Mutation Taster
=100/0
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

Publications

Other links and lift over

dbSNP: rs7733241; hg19: chr5-151208890; API