chr5-151822739-G-A

Position:

• chr5-151822739-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000171.4(GLRA1):​c.1284C>T​(p.Leu428Leu) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GLRA1 NM_000171.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.93

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 5-151822739-G-A is Benign according to our data. Variant chr5-151822739-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 761119.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLRA1	NM_000171.4	c.1284C>T	p.Leu428Leu	synonymous_variant	9/9	ENST00000274576.9	NP_000162.2
GLRA1	NM_001146040.2	c.1308C>T	p.Leu436Leu	synonymous_variant	9/9		NP_001139512.1
GLRA1	NM_001292000.2	c.1035C>T	p.Leu345Leu	synonymous_variant	8/8		NP_001278929.1
GLRA1	XM_047417105.1	c.1332C>T	p.Leu444Leu	synonymous_variant	9/9		XP_047273061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLRA1	ENST00000274576.9	c.1284C>T	p.Leu428Leu	synonymous_variant	9/9	1	NM_000171.4	ENSP00000274576.5
GLRA1	ENST00000455880.2	c.1308C>T	p.Leu436Leu	synonymous_variant	9/9	1		ENSP00000411593.2
GLRA1	ENST00000462581.6	n.*1042C>T		non_coding_transcript_exon_variant	8/8	1		ENSP00000430595.1
GLRA1	ENST00000462581.6	n.*1042C>T		3_prime_UTR_variant	8/8	1		ENSP00000430595.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary hyperekplexia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 11, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.2
DANN	Benign	0.75

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: rs1581592341; hg19: chr5-151202300;