rs7655209

Variant names:

• chr4-157130233-G-A
• rs7655209
• NM_000824.5:c.298-6236G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000824.5(GLRB):​c.298-6236G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,424 control chromosomes in the GnomAD database, including 8,172 homozygotes. 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: 𝑓 0.27 (8172 hom., cov: 32)
• Consequence: GLRB NM_000824.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643
• Publications: 9 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

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.298-6236G>A		intron	N/A	NP_000815.1	P48167-1
	GLRB	NM_001166060.2		c.298-6236G>A		intron	N/A	NP_001159532.1	P48167-1
	GLRB	NM_001440545.1		c.4-6236G>A		intron	N/A	NP_001427474.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRB	ENST00000264428.9	TSL:1 MANE Select	c.298-6236G>A		intron	N/A	ENSP00000264428.4	P48167-1
	GLRB	ENST00000509282.1	TSL:1	c.298-6236G>A		intron	N/A	ENSP00000427186.1	P48167-1
	GLRB	ENST00000960009.1		c.298-6236G>A		intron	N/A	ENSP00000630068.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41260 AN: 151304 Hom.: 8134 Cov.: 32

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.273 AC: 41351 AN: 151424 Hom.: 8172 Cov.: 32 AF XY: 0.266 AC XY: 19656 AN XY: 74000

African (AFR) AF: 0.563 AC: 23308 AN: 41364

American (AMR) AF: 0.172 AC: 2607 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 616 AN: 3464

East Asian (EAS) AF: 0.154 AC: 786 AN: 5090

South Asian (SAS) AF: 0.179 AC: 862 AN: 4814

European-Finnish (FIN) AF: 0.120 AC: 1276 AN: 10596

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11214 AN: 67636

Other (OTH) AF: 0.244 AC: 513 AN: 2102

Alfa AF: 0.196 Hom.: 12116

Bravo AF: 0.290

Asia WGS AF: 0.189 AC: 655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.31
DANN	Benign	0.36
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7655209; hg19: chr4-158051385;