NM_006529.4:c.200-8363T>C

Variant names:

• chr4-174775393-A-G
• rs1385838
• NM_006529.4:c.200-8363T>C

Variant summary

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

The NM_006529.4(GLRA3):​c.200-8363T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,078 control chromosomes in the GnomAD database, including 41,187 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 0.73 (41187 hom., cov: 31)
• Consequence: GLRA3 NM_006529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRA3	NM_006529.4	c.200-8363T>C		intron_variant	Intron 2 of 9	ENST00000274093.8	NP_006520.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRA3	ENST00000274093.8	c.200-8363T>C		intron_variant	Intron 2 of 9	1	NM_006529.4	ENSP00000274093.3
GLRA3	ENST00000340217.5	c.200-8363T>C		intron_variant	Intron 2 of 8	1		ENSP00000345284.5

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111431 AN: 151960 Hom.: 41153 Cov.: 31

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.733 AC: 111514 AN: 152078 Hom.: 41187 Cov.: 31 AF XY: 0.736 AC XY: 54719 AN XY: 74340

African (AFR) AF: 0.679 AC: 28168 AN: 41484

American (AMR) AF: 0.709 AC: 10835 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2700 AN: 3472

East Asian (EAS) AF: 0.995 AC: 5144 AN: 5172

South Asian (SAS) AF: 0.780 AC: 3760 AN: 4822

European-Finnish (FIN) AF: 0.744 AC: 7859 AN: 10560

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.746 AC: 50723 AN: 67984

Other (OTH) AF: 0.744 AC: 1565 AN: 2104

Alfa AF: 0.740 Hom.: 67300

Bravo AF: 0.729

Asia WGS AF: 0.855 AC: 2973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.61
PhyloP100		-0.31
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: rs1385838; hg19: chr4-175696544;