rs7733241

Positions:

• chr5-151829329-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.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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLRA1	NM_000171.4	c.913-262A>G		intron_variant		ENST00000274576.9	NP_000162.2
GLRA1	NM_001146040.2	c.913-262A>G		intron_variant			NP_001139512.1
GLRA1	NM_001292000.2	c.664-262A>G		intron_variant			NP_001278929.1
GLRA1	XM_047417105.1	c.961-262A>G		intron_variant			XP_047273061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLRA1	ENST00000274576.9	c.913-262A>G		intron_variant		1	NM_000171.4	ENSP00000274576	P4
GLRA1	ENST00000455880.2	c.913-262A>G		intron_variant		1		ENSP00000411593	A1
GLRA1	ENST00000462581.6	c.*671-262A>G		intron_variant, NMD_transcript_variant		1		ENSP00000430595

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

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.444

Alfa AF: 0.447 Hom.: 2534

Bravo AF: 0.467

Asia WGS AF: 0.447 AC: 1551 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 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.78

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: rs7733241; hg19: chr5-151208890;