dbSNP rs6814940: GLRB:c.751+701T>A (chr4-157139650-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.687

Publications

0 publications found

Variant links:

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

GLRB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GLRB	NM_000824.5 link	c.751+701T>A		intron_variant	Intron 7 of 9	ENST00000264428.9	NP_000815.1	P48167-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GLRB	ENST00000264428.9 link	c.751+701T>A	intron_variant	Intron 7 of 9	1	NM_000824.5	ENSP00000264428.4	P48167-1
GLRB	ENST00000509282.1 link	c.751+701T>A	intron_variant	Intron 7 of 9	1		ENSP00000427186.1	P48167-1
GLRB	ENST00000541722.5 link	c.751+701T>A	intron_variant	Intron 7 of 8	5		ENSP00000441873.1	P48167-2
GLRB	ENST00000512619.5 link	c.123-30782T>A	intron_variant	Intron 2 of 2	3		ENSP00000425433.1	D6RD86

Frequencies

GnomAD3 genomes

AF:

0.0856

AC:

13009

AN:

151914

Hom.:

1507

Cov.:

show subpopulations

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.:

AF XY:

0.0818

AC XY:

6081

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.273

AC:

11337

AN:

41486

American (AMR)

AF:

0.0457

AC:

698

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0159

AC:

AN:

3466

East Asian (EAS)

AF:

0.000580

AC:

AN:

5176

South Asian (SAS)

AF:

0.00890

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00207

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0114

AC:

777

AN:

67882

Other (OTH)

AF:

0.0655

AC:

138

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

514

1029

1543

2058

2572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.73

PhyloP100

0.69

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over