rs1465555

chr5-151910137-T-C

Variant summary

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

The NM_000171.4(GLRA1):c.56+14357A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,038 control chromosomes in the GnomAD database, including 40,872 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 0.73 (40872 hom., cov: 31)
• Consequence: GLRA1 NM_000171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.571

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLRA1	NM_000171.4	c.56+14357A>G		intron_variant		ENST00000274576.9
GLRA1	NM_001146040.2	c.56+14357A>G		intron_variant
GLRA1	NM_001292000.2	c.-66+14357A>G		intron_variant
GLRA1	XM_047417105.1	c.54+78A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLRA1	ENST00000274576.9	c.56+14357A>G		intron_variant		1	NM_000171.4	P4
GLRA1	ENST00000455880.2	c.56+14357A>G		intron_variant		1		A1
GLRA1	ENST00000462581.6	c.56+14357A>G		intron_variant, NMD_transcript_variant		1
GLRA1	ENST00000471351.2	n.339+14357A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110370 AN: 151920 Hom.: 40815 Cov.: 31

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.691

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.727 AC: 110485 AN: 152038 Hom.: 40872 Cov.: 31 AF XY: 0.723 AC XY: 53724 AN XY: 74320

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.704

Alfa AF: 0.679 Hom.: 52592

Bravo AF: 0.742

Asia WGS AF: 0.665 AC: 2314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	9.3
Dann	Benign	0.73

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: rs1465555; hg19: chr5-151289698; COSMIC: COSV51009003;