rs76872663

chr5-151851579-C-Achr5-151851579-C-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_000171.4(GLRA1):c.723G>T(p.Arg241=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R241R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLRA1 NM_000171.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=-1.13 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLRA1	NM_000171.4	c.723G>T	p.Arg241=	synonymous_variant	7/9	ENST00000274576.9
GLRA1	NM_001146040.2	c.723G>T	p.Arg241=	synonymous_variant	7/9
GLRA1	NM_001292000.2	c.474G>T	p.Arg158=	synonymous_variant	6/8
GLRA1	XM_047417105.1	c.771G>T	p.Arg257=	synonymous_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLRA1	ENST00000274576.9	c.723G>T	p.Arg241=	synonymous_variant	7/9	1	NM_000171.4	P4
GLRA1	ENST00000455880.2	c.723G>T	p.Arg241=	synonymous_variant	7/9	1		A1
GLRA1	ENST00000471351.2	n.1006G>T		non_coding_transcript_exon_variant	7/8	1
GLRA1	ENST00000462581.6	c.*481G>T		3_prime_UTR_variant, NMD_transcript_variant	6/8	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	6.2
Dann	Benign	0.59

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: rs76872663; hg19: chr5-151231140;