5-151822730-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_000171.4(GLRA1):c.1293C>T(p.Asn431=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000958 in 1,461,576 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 (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: GLRA1 NM_000171.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.71

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 5-151822730-G-A is Benign according to our data. Variant chr5-151822730-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1109235.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLRA1	NM_000171.4	c.1293C>T	p.Asn431=	synonymous_variant	9/9	ENST00000274576.9
GLRA1	NM_001146040.2	c.1317C>T	p.Asn439=	synonymous_variant	9/9
GLRA1	NM_001292000.2	c.1044C>T	p.Asn348=	synonymous_variant	8/8
GLRA1	XM_047417105.1	c.1341C>T	p.Asn447=	synonymous_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLRA1	ENST00000274576.9	c.1293C>T	p.Asn431=	synonymous_variant	9/9	1	NM_000171.4	P4
GLRA1	ENST00000455880.2	c.1317C>T	p.Asn439=	synonymous_variant	9/9	1		A1
GLRA1	ENST00000462581.6	c.*1051C>T		3_prime_UTR_variant, NMD_transcript_variant	8/8	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461576 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 727120

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary hyperekplexia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 29, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	6.6
Dann	Benign	0.68

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: rs1763170405; hg19: chr5-151202291;