NM_000171.4:c.913-262A>G

Variant names:

• chr5-151829329-T-C
• rs7733241
• NM_000171.4:c.913-262A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000171.4(GLRA1):​c.913-262A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,034 control chromosomes in the GnomAD database, including 17,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.47 (17281 hom., cov: 32)
• Consequence: GLRA1 NM_000171.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.839
• Publications: 2 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: Labcorp Genetics (formerly Invitae), G2P
• hereditary hyperekplexia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 5-151829329-T-C is Benign according to our data. Variant chr5-151829329-T-C is described in ClinVar as Benign. ClinVar VariationId is 1283942.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 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.913-262A>G		intron	N/A	NP_000162.2	P23415-2
	GLRA1	NM_001146040.2		c.913-262A>G		intron	N/A	NP_001139512.1	P23415-1
	GLRA1	NM_001292000.2		c.664-262A>G		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.913-262A>G		intron	N/A	ENSP00000274576.5	P23415-2
	GLRA1	ENST00000455880.2	TSL:1	c.913-262A>G		intron	N/A	ENSP00000411593.2	P23415-1
	GLRA1	ENST00000462581.6	TSL:1	n.*671-262A>G		intron	N/A	ENSP00000430595.1	E5RJ70

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70755 AN: 151916 Hom.: 17246 Cov.: 32

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.466 AC: 70837 AN: 152034 Hom.: 17281 Cov.: 32 AF XY: 0.463 AC XY: 34408 AN XY: 74298

African (AFR) AF: 0.621 AC: 25746 AN: 41464

American (AMR) AF: 0.390 AC: 5954 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1268 AN: 3470

East Asian (EAS) AF: 0.320 AC: 1654 AN: 5174

South Asian (SAS) AF: 0.465 AC: 2244 AN: 4822

European-Finnish (FIN) AF: 0.419 AC: 4424 AN: 10554

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28236 AN: 67974

Other (OTH) AF: 0.444 AC: 936 AN: 2108

Alfa AF: 0.446 Hom.: 5185

Bravo AF: 0.467

Asia WGS AF: 0.447 AC: 1551 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.78
PhyloP100		-0.84
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: rs7733241; hg19: chr5-151208890;