rs6814940

Positions:

• chr4-157139650-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000824.5(GLRB):​c.751+701T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0861 in 152,030 control chromosomes in the GnomAD database, including 1,536 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 0.086 (1536 hom., cov: 32)
• Consequence: GLRB NM_000824.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.687

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLRB	NM_000824.5	c.751+701T>A		intron_variant		ENST00000264428.9	NP_000815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLRB	ENST00000264428.9	c.751+701T>A		intron_variant		1	NM_000824.5	ENSP00000264428	P1
GLRB	ENST00000509282.1	c.751+701T>A		intron_variant		1		ENSP00000427186	P1
GLRB	ENST00000512619.5	c.123-30782T>A		intron_variant		3		ENSP00000425433
GLRB	ENST00000541722.5	c.751+701T>A		intron_variant		5		ENSP00000441873

Frequencies

GnomAD3 genomes AF: 0.0856 AC: 13009 AN: 151914 Hom.: 1507 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0458

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00910

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.0662

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

GnomAD4 genome AF: 0.0861 AC: 13084 AN: 152030 Hom.: 1536 Cov.: 32 AF XY: 0.0818 AC XY: 6081 AN XY: 74310

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.0457

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.00890

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.0114

Gnomad4 OTH AF: 0.0655

Alfa AF: 0.0548 Hom.: 115

Bravo AF: 0.0994

Asia WGS AF: 0.0280 AC: 100 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.73

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: rs6814940; hg19: chr4-158060802;