NM_000824.5:c.798C>A

Variant names:

• chr4-157143853-C-A
• rs148773767
• NM_000824.5:c.798C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000824.5(GLRB):​c.798C>A​(p.Val266Val) 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. V266V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLRB NM_000824.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110
• Publications: 0 publications found

Genes affected

GLRB (HGNC:4329): (glycine receptor beta) This gene encodes the beta subunit of the glycine receptor, which is a pentamer composed of alpha and beta subunits. The receptor functions as a neurotransmitter-gated ion channel, which produces hyperpolarization via increased chloride conductance due to the binding of glycine to the receptor. Mutations in this gene cause startle disease, also known as hereditary hyperekplexia or congenital stiff-person syndrome, a disease characterized by muscular rigidity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

GLRB Gene-Disease associations (from GenCC):

• hyperekplexia 2

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• hereditary hyperekplexia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000824.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRB	NM_000824.5	MANE Select	c.798C>A	p.Val266Val	synonymous	Exon 8 of 10	NP_000815.1	P48167-1
	GLRB	NM_001166060.2		c.798C>A	p.Val266Val	synonymous	Exon 8 of 10	NP_001159532.1	P48167-1
	GLRB	NM_001440545.1		c.504C>A	p.Val168Val	synonymous	Exon 9 of 11	NP_001427474.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRB	ENST00000264428.9	TSL:1 MANE Select	c.798C>A	p.Val266Val	synonymous	Exon 8 of 10	ENSP00000264428.4	P48167-1
	GLRB	ENST00000509282.1	TSL:1	c.798C>A	p.Val266Val	synonymous	Exon 8 of 10	ENSP00000427186.1	P48167-1
	GLRB	ENST00000960009.1		c.798C>A	p.Val266Val	synonymous	Exon 8 of 11	ENSP00000630068.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.082
DANN	Benign	0.69
PhyloP100		-0.011

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.49		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.49		Position offset: -46

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs148773767; hg19: chr4-158065005;