rs10857299

chr4-157078376-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000824.5(GLRB):c.122+230T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 231,340 control chromosomes in the GnomAD database, including 4,992 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3526 hom., cov: 31)
  • Exomes 𝑓: 0.18 (1466 hom.)
• Consequence: GLRB NM_000824.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.335

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 4-157078376-T-C is Benign according to our data. Variant chr4-157078376-T-C is described in ClinVar as [Benign]. Clinvar id is 1242317.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLRB	NM_000824.5	c.122+230T>C		intron_variant		ENST00000264428.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLRB	ENST00000264428.9	c.122+230T>C		intron_variant		1	NM_000824.5	P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 31989 AN: 151464 Hom.: 3525 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.183 AC: 14587 AN: 79764 Hom.: 1466 AF XY: 0.182 AC XY: 7023 AN XY: 38626

Gnomad4 AFR exome AF: 0.221

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.221

Gnomad4 EAS exome AF: 0.346

Gnomad4 SAS exome AF: 0.367

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.211 AC: 32002 AN: 151576 Hom.: 3526 Cov.: 31 AF XY: 0.213 AC XY: 15790 AN XY: 74098

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.204

Alfa AF: 0.190 Hom.: 827

Bravo AF: 0.210

Asia WGS AF: 0.324 AC: 1121 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.7
Dann	Benign	0.77

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: rs10857299; hg19: chr4-157999528;