rs2964608

Variant names:

• chr5-151897328-G-A
• rs2964608
• NM_000171.4:c.57-4890C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-151897328-G-A
• chr5-151897328-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

GLRA1 Gene-Disease associations (from GenCC):

• hyperekplexia 1

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000171.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRA1	NM_000171.4	MANE Select	c.57-4890C>T		intron	N/A	NP_000162.2	P23415-2
	GLRA1	NM_001146040.2		c.57-4890C>T		intron	N/A	NP_001139512.1	P23415-1
	GLRA1	NM_001292000.2		c.-65-10540C>T		intron	N/A	NP_001278929.1	Q14C71

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRA1	ENST00000274576.9	TSL:1 MANE Select	c.57-4890C>T		intron	N/A	ENSP00000274576.5	P23415-2
	GLRA1	ENST00000455880.2	TSL:1	c.57-4890C>T		intron	N/A	ENSP00000411593.2	P23415-1
	GLRA1	ENST00000462581.6	TSL:1	n.57-10540C>T		intron	N/A	ENSP00000430595.1	E5RJ70

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

African (AFR) AF: 0.443 AC: 18367 AN: 41416

American (AMR) AF: 0.361 AC: 5524 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3470

East Asian (EAS) AF: 0.353 AC: 1822 AN: 5158

South Asian (SAS) AF: 0.476 AC: 2297 AN: 4824

European-Finnish (FIN) AF: 0.478 AC: 5044 AN: 10548

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25595 AN: 67972

Other (OTH) AF: 0.391 AC: 820 AN: 2098

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
DANN	Benign	0.35
PhyloP100		0.72
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: rs2964608; hg19: chr5-151276889;