rs768970494

Variant names:

• chr5-151822862-G-A
• rs768970494
• NM_000171.4:c.1161C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-151822862-G-A
• chr5-151822862-G-C

Variant summary

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

The NM_000171.4(GLRA1):​c.1161C>T​(p.Asn387Asn) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GLRA1 NM_000171.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.29

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRA1	NM_000171.4	c.1161C>T	p.Asn387Asn	synonymous_variant	Exon 9 of 9	ENST00000274576.9	NP_000162.2
GLRA1	NM_001146040.2	c.1185C>T	p.Asn395Asn	synonymous_variant	Exon 9 of 9		NP_001139512.1
GLRA1	NM_001292000.2	c.912C>T	p.Asn304Asn	synonymous_variant	Exon 8 of 8		NP_001278929.1
GLRA1	XM_047417105.1	c.1209C>T	p.Asn403Asn	synonymous_variant	Exon 9 of 9		XP_047273061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRA1	ENST00000274576.9	c.1161C>T	p.Asn387Asn	synonymous_variant	Exon 9 of 9	1	NM_000171.4	ENSP00000274576.5
GLRA1	ENST00000455880.2	c.1185C>T	p.Asn395Asn	synonymous_variant	Exon 9 of 9	1		ENSP00000411593.2
GLRA1	ENST00000462581.6	n.*919C>T		non_coding_transcript_exon_variant	Exon 8 of 8	1		ENSP00000430595.1
GLRA1	ENST00000462581.6	n.*919C>T		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000430595.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251322 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135822

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	1.3
DANN	Benign	0.63

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: rs768970494; hg19: chr5-151202423;