rs575951950
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS1
The NM_000171.4(GLRA1):āc.459T>Cā(p.Asn153=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,612,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.000053 ( 0 hom., cov: 32)
Exomes š: 0.00014 ( 0 hom. )
Consequence
GLRA1
NM_000171.4 synonymous
NM_000171.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.119
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 5-151859802-A-G is Benign according to our data. Variant chr5-151859802-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 464188.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.119 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000525 (8/152268) while in subpopulation SAS AF= 0.00166 (8/4824). AF 95% confidence interval is 0.000825. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLRA1 | NM_000171.4 | c.459T>C | p.Asn153= | synonymous_variant | 4/9 | ENST00000274576.9 | |
GLRA1 | NM_001146040.2 | c.459T>C | p.Asn153= | synonymous_variant | 4/9 | ||
GLRA1 | NM_001292000.2 | c.210T>C | p.Asn70= | synonymous_variant | 3/8 | ||
GLRA1 | XM_047417105.1 | c.507T>C | p.Asn169= | synonymous_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLRA1 | ENST00000274576.9 | c.459T>C | p.Asn153= | synonymous_variant | 4/9 | 1 | NM_000171.4 | P4 | |
GLRA1 | ENST00000455880.2 | c.459T>C | p.Asn153= | synonymous_variant | 4/9 | 1 | A1 | ||
GLRA1 | ENST00000471351.2 | n.742T>C | non_coding_transcript_exon_variant | 4/8 | 1 | ||||
GLRA1 | ENST00000462581.6 | c.*217T>C | 3_prime_UTR_variant, NMD_transcript_variant | 3/8 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152150Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000310 AC: 78AN: 251364Hom.: 0 AF XY: 0.000412 AC XY: 56AN XY: 135872
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GnomAD4 exome AF: 0.000142 AC: 208AN: 1460274Hom.: 0 Cov.: 32 AF XY: 0.000204 AC XY: 148AN XY: 726592
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GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152268Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74444
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary hyperekplexia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 22, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at