rs62636580
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000171.4(GLRA1):c.1224C>T(p.Phe408=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0044 in 1,614,090 control chromosomes in the GnomAD database, including 272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.023 ( 137 hom., cov: 31)
Exomes 𝑓: 0.0024 ( 135 hom. )
Consequence
GLRA1
NM_000171.4 synonymous
NM_000171.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.52
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant 5-151822799-G-A is Benign according to our data. Variant chr5-151822799-G-A is described in ClinVar as [Benign]. Clinvar id is 352306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=3.52 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0787 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLRA1 | NM_000171.4 | c.1224C>T | p.Phe408= | synonymous_variant | 9/9 | ENST00000274576.9 | |
GLRA1 | NM_001146040.2 | c.1248C>T | p.Phe416= | synonymous_variant | 9/9 | ||
GLRA1 | NM_001292000.2 | c.975C>T | p.Phe325= | synonymous_variant | 8/8 | ||
GLRA1 | XM_047417105.1 | c.1272C>T | p.Phe424= | synonymous_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLRA1 | ENST00000274576.9 | c.1224C>T | p.Phe408= | synonymous_variant | 9/9 | 1 | NM_000171.4 | P4 | |
GLRA1 | ENST00000455880.2 | c.1248C>T | p.Phe416= | synonymous_variant | 9/9 | 1 | A1 | ||
GLRA1 | ENST00000462581.6 | c.*982C>T | 3_prime_UTR_variant, NMD_transcript_variant | 8/8 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0232 AC: 3536AN: 152152Hom.: 135 Cov.: 31
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GnomAD3 exomes AF: 0.00590 AC: 1484AN: 251412Hom.: 56 AF XY: 0.00411 AC XY: 558AN XY: 135876
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GnomAD4 exome AF: 0.00243 AC: 3548AN: 1461820Hom.: 135 Cov.: 31 AF XY: 0.00209 AC XY: 1519AN XY: 727218
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GnomAD4 genome ? AF: 0.0233 AC: 3554AN: 152270Hom.: 137 Cov.: 31 AF XY: 0.0222 AC XY: 1655AN XY: 74458
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hyperekplexia 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 11, 2018 | - - |
Hereditary hyperekplexia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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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