chr4-174730348-T-C

Variant names:

• chr4-174730348-T-C
• rs1564939
• NM_006529.4:c.268-1650A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006529.4(GLRA3):​c.268-1650A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,114 control chromosomes in the GnomAD database, including 2,941 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 0.19 (2941 hom., cov: 32)
• Consequence: GLRA3 NM_006529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 8 publications found

Genes affected

GLRA3 (HGNC:4328): (glycine receptor alpha 3) This gene encodes a member of the ligand-gated ion channel protein family. The encoded protein is a member of the glycine receptor subfamily. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRA3	NM_006529.4	c.268-1650A>G		intron_variant	Intron 3 of 9	ENST00000274093.8	NP_006520.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRA3	ENST00000274093.8	c.268-1650A>G		intron_variant	Intron 3 of 9	1	NM_006529.4	ENSP00000274093.3
GLRA3	ENST00000340217.5	c.268-1650A>G		intron_variant	Intron 3 of 8	1		ENSP00000345284.5

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29250 AN: 151996 Hom.: 2937 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.192 AC: 29269 AN: 152114 Hom.: 2941 Cov.: 32 AF XY: 0.193 AC XY: 14357 AN XY: 74382

African (AFR) AF: 0.144 AC: 5994 AN: 41508

American (AMR) AF: 0.217 AC: 3311 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 892 AN: 3470

East Asian (EAS) AF: 0.319 AC: 1646 AN: 5160

South Asian (SAS) AF: 0.144 AC: 695 AN: 4828

European-Finnish (FIN) AF: 0.162 AC: 1711 AN: 10580

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14402 AN: 67976

Other (OTH) AF: 0.186 AC: 393 AN: 2110

Alfa AF: 0.203 Hom.: 1632

Bravo AF: 0.196

Asia WGS AF: 0.207 AC: 718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.31
DANN	Benign	0.34
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1564939; hg19: chr4-175651499;