NM_000171.4:c.184+1542C>A

Variant names:

• chr5-151890769-G-T
• NM_000171.4:c.184+1542C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000171.4(GLRA1):​c.184+1542C>A variant causes a intron 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.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GLRA1 NM_000171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRA1	NM_000171.4	c.184+1542C>A		intron_variant	Intron 2 of 8	ENST00000274576.9	NP_000162.2
GLRA1	NM_001146040.2	c.184+1542C>A		intron_variant	Intron 2 of 8		NP_001139512.1
GLRA1	NM_001292000.2	c.-65-3981C>A		intron_variant	Intron 1 of 7		NP_001278929.1
GLRA1	XM_047417105.1	c.232+1542C>A		intron_variant	Intron 2 of 8		XP_047273061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRA1	ENST00000274576.9	c.184+1542C>A		intron_variant	Intron 2 of 8	1	NM_000171.4	ENSP00000274576.5
GLRA1	ENST00000455880.2	c.184+1542C>A		intron_variant	Intron 2 of 8	1		ENSP00000411593.2
GLRA1	ENST00000462581.6	n.57-3981C>A		intron_variant	Intron 1 of 7	1		ENSP00000430595.1
GLRA1	ENST00000471351.2	n.467+1542C>A		intron_variant	Intron 2 of 7	1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.16
DANN	Benign	0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-151270330;