rs6630716

Positions:

• chrX-14616743-C-T

Variant summary

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

The NM_002063.4(GLRA2):​c.930+7538C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 111,151 control chromosomes in the GnomAD database, including 2,487 homozygotes. There are 7,925 hemizygotes in GnomAD. 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 0.24 (2487 hom., 7925 hem., cov: 23)
• Consequence: GLRA2 NM_002063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.763

Genes affected

GLRA2 (HGNC:4327): (glycine receptor alpha 2) The glycine receptor consists of two subunits, alpha and beta, and acts as a pentamer. The protein encoded by this gene is an alpha subunit and can bind strychnine. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLRA2	NM_002063.4	c.930+7538C>T		intron_variant		ENST00000218075.9	NP_002054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLRA2	ENST00000218075.9	c.930+7538C>T		intron_variant		1	NM_002063.4	ENSP00000218075	A1
GLRA2	ENST00000355020.9	c.930+7538C>T		intron_variant		1		ENSP00000347123	P4
GLRA2	ENST00000443437.6	c.*857+7538C>T		intron_variant, NMD_transcript_variant		2		ENSP00000387756
GLRA2	ENST00000415367.2	n.1181+7538C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.242 AC: 26939 AN: 111098 Hom.: 2487 Cov.: 23 AF XY: 0.237 AC XY: 7916 AN XY: 33426

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0113

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.233

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.242 AC: 26948 AN: 111151 Hom.: 2487 Cov.: 23 AF XY: 0.237 AC XY: 7925 AN XY: 33489

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.0113

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.223

Alfa AF: 0.271 Hom.: 4430

Bravo AF: 0.229

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.5
DANN	Benign	0.53

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: rs6630716; hg19: chrX-14634865; COSMIC: COSV99491098;