rs2964608

chr5-151897328-G-Achr5-151897328-G-C

Variant summary

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

The NM_000171.4(GLRA1):c.57-4890C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,982 control chromosomes in the GnomAD database, including 12,446 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 0.40 (12446 hom., cov: 32)
• Consequence: GLRA1 NM_000171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.718

Genes affected

GLRA1 (HGNC:4326): (glycine receptor alpha 1) The protein encoded by this gene is a subunit of a pentameric inhibitory glycine receptor, which mediates postsynaptic inhibition in the central nervous system. Defects in this gene are a cause of startle disease (STHE), also known as hereditary hyperekplexia or congenital stiff-person syndrome. Multiple transcript variants encoding different isoforms have been found. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLRA1	NM_000171.4	c.57-4890C>T		intron_variant		ENST00000274576.9
GLRA1	NM_001146040.2	c.57-4890C>T		intron_variant
GLRA1	NM_001292000.2	c.-65-10540C>T		intron_variant
GLRA1	XM_047417105.1	c.55-4840C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLRA1	ENST00000274576.9	c.57-4890C>T		intron_variant		1	NM_000171.4	P4
GLRA1	ENST00000455880.2	c.57-4890C>T		intron_variant		1		A1
GLRA1	ENST00000462581.6	c.57-10540C>T		intron_variant, NMD_transcript_variant		1
GLRA1	ENST00000471351.2	n.340-4890C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61084 AN: 151864 Hom.: 12427 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.402 AC: 61142 AN: 151982 Hom.: 12446 Cov.: 32 AF XY: 0.407 AC XY: 30216 AN XY: 74292

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.391

Alfa AF: 0.383 Hom.: 1387

Bravo AF: 0.394

Asia WGS AF: 0.421 AC: 1460 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.7
Dann	Benign	0.35

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: rs2964608; hg19: chr5-151276889;