rs3848874

Variant names:

• chrX-123439534-G-A
• rs3848874
• NM_000828.5:c.2076+11395G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-123439534-G-A
• chrX-123439534-G-T

Variant summary

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

The NM_007325.5(GRIA3):​c.2076+11395G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 109,129 control chromosomes in the GnomAD database, including 2,389 homozygotes. There are 6,312 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 0.21 (2389 hom., 6312 hem., cov: 22)
• Consequence: GRIA3 NM_007325.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388

Genes affected

GRIA3 (HGNC:4573): (glutamate ionotropic receptor AMPA type subunit 3) Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. These receptors are heteromeric protein complexes composed of multiple subunits, arranged to form ligand-gated ion channels. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. The subunit encoded by this gene belongs to a family of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate)-sensitive glutamate receptors, and is subject to RNA editing (AGA->GGA; R->G). Alternative splicing at this locus results in different isoforms, which may vary in their signal transduction properties. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA3	NM_000828.5	c.2076+11395G>A		intron_variant	Intron 12 of 15	ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.2076+11395G>A		intron_variant	Intron 12 of 15	ENST00000620443.2	NP_015564.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2	c.2076+11395G>A		intron_variant	Intron 12 of 15	1	NM_007325.5	ENSP00000478489.1
GRIA3	ENST00000622768.5	c.2076+11395G>A		intron_variant	Intron 12 of 15	5	NM_000828.5	ENSP00000481554.1
GRIA3	ENST00000620581.4	n.2076+11395G>A		intron_variant	Intron 12 of 16	1		ENSP00000481875.1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 23331 AN: 109103 Hom.: 2391 Cov.: 22 AF XY: 0.198 AC XY: 6281 AN XY: 31703

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0493

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.128

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.214 AC: 23356 AN: 109129 Hom.: 2389 Cov.: 22 AF XY: 0.199 AC XY: 6312 AN XY: 31741

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.0497

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.210

Alfa AF: 0.172 Hom.: 973

Bravo AF: 0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.76

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: rs3848874; hg19: chrX-122573385;