rs919262

Positions:

• chr5-151886523-T-C

Variant summary

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

The NM_000171.4(GLRA1):​c.252+198A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,170 control chromosomes in the GnomAD database, including 4,824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.24 (4824 hom., cov: 33)
• Consequence: GLRA1 NM_000171.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.90

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 5-151886523-T-C is Benign according to our data. Variant chr5-151886523-T-C is described in ClinVar as [Benign]. Clinvar id is 1243022.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLRA1	NM_000171.4	c.252+198A>G		intron_variant		ENST00000274576.9	NP_000162.2
GLRA1	NM_001146040.2	c.252+198A>G		intron_variant			NP_001139512.1
GLRA1	NM_001292000.2	c.3+198A>G		intron_variant			NP_001278929.1
GLRA1	XM_047417105.1	c.300+198A>G		intron_variant			XP_047273061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLRA1	ENST00000274576.9	c.252+198A>G		intron_variant		1	NM_000171.4	ENSP00000274576.5
GLRA1	ENST00000455880.2	c.252+198A>G		intron_variant		1		ENSP00000411593.2
GLRA1	ENST00000462581.6	n.*10+198A>G		intron_variant		1		ENSP00000430595.1
GLRA1	ENST00000471351.2	n.535+198A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 37022 AN: 152052 Hom.: 4816 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.243 AC: 37053 AN: 152170 Hom.: 4824 Cov.: 33 AF XY: 0.248 AC XY: 18467 AN XY: 74392

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.235

Alfa AF: 0.250 Hom.: 1793

Bravo AF: 0.233

Asia WGS AF: 0.364 AC: 1264 AN: 3478

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

Jul 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.86
DANN	Benign	0.66

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: rs919262; hg19: chr5-151266084;