chr4-157093826-G-C

Variant names:

• chr4-157093826-G-C
• rs11930311
• NM_000824.5:c.122+15680G>C

Variant summary

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

The NM_000824.5(GLRB):​c.122+15680G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 150,058 control chromosomes in the GnomAD database, including 4,957 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 0.25 (4957 hom., cov: 30)
• Consequence: GLRB NM_000824.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655
• Publications: 6 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, G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRB	NM_000824.5	c.122+15680G>C		intron_variant	Intron 2 of 9	ENST00000264428.9	NP_000815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRB	ENST00000264428.9	c.122+15680G>C		intron_variant	Intron 2 of 9	1	NM_000824.5	ENSP00000264428.4

Frequencies

GnomAD3 genomes AF: 0.247 AC: 36983 AN: 149978 Hom.: 4953 Cov.: 30

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.327

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.247 AC: 37004 AN: 150058 Hom.: 4957 Cov.: 30 AF XY: 0.249 AC XY: 18182 AN XY: 73056

African (AFR) AF: 0.323 AC: 13127 AN: 40698

American (AMR) AF: 0.208 AC: 3131 AN: 15064

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 853 AN: 3460

East Asian (EAS) AF: 0.421 AC: 2142 AN: 5090

South Asian (SAS) AF: 0.401 AC: 1898 AN: 4730

European-Finnish (FIN) AF: 0.188 AC: 1873 AN: 9980

Middle Eastern (MID) AF: 0.329 AC: 92 AN: 280

European-Non Finnish (NFE) AF: 0.194 AC: 13159 AN: 67766

Other (OTH) AF: 0.245 AC: 509 AN: 2080

Alfa AF: 0.0804 Hom.: 80

Bravo AF: 0.249

Asia WGS AF: 0.363 AC: 1258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.51
DANN	Benign	0.79
PhyloP100		-0.66
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: rs11930311; hg19: chr4-158014978;