rs7695870

Variant names:

• chr4-157342624-G-A
• rs7695870
• NM_001083619.3:c.2043+1162G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-157342624-G-A
• chr4-157342624-G-T

Variant summary

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

The NM_001083619.3(GRIA2):​c.2043+1162G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 186,854 control chromosomes in the GnomAD database, including 4,277 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 (4111 hom., cov: 32)
  • Exomes 𝑓: 0.080 (166 hom.)
• Consequence: GRIA2 NM_001083619.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• Publications: 5 publications found

Genes affected

GRIA2 (HGNC:4572): (glutamate ionotropic receptor AMPA type subunit 2) Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to a family of glutamate receptors that are sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and function as ligand-activated cation channels. These channels are assembled from 4 related subunits, GRIA1-4. The subunit encoded by this gene (GRIA2) is subject to RNA editing (CAG->CGG; Q->R) within the second transmembrane domain, which is thought to render the channel impermeable to Ca(2+). Human and animal studies suggest that pre-mRNA editing is essential for brain function, and defective GRIA2 RNA editing at the Q/R site may be relevant to amyotrophic lateral sclerosis (ALS) etiology. Alternative splicing, resulting in transcript variants encoding different isoforms, (including the flip and flop isoforms that vary in their signal transduction properties), has been noted for this gene. [provided by RefSeq, Jul 2008]

GRIA2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with language impairment and behavioral abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, ClinGen, Illumina, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083619.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA2	NM_001083619.3	MANE Select	c.2043+1162G>A		intron	N/A	NP_001077088.2	P42262-1
	GRIA2	NM_000826.6		c.2043+1162G>A		intron	N/A	NP_000817.5	P42262-2
	GRIA2	NM_001083620.3		c.1902+1162G>A		intron	N/A	NP_001077089.2	P42262-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA2	ENST00000264426.14	TSL:1 MANE Select	c.2043+1162G>A		intron	N/A	ENSP00000264426.9	P42262-1
	GRIA2	ENST00000296526.12	TSL:1	c.2043+1162G>A		intron	N/A	ENSP00000296526.7	P42262-2
	GRIA2	ENST00000393815.6	TSL:1	c.1902+1162G>A		intron	N/A	ENSP00000377403.2	P42262-4

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28109 AN: 151690 Hom.: 4098 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0504

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.0885

Gnomad FIN AF: 0.0801

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0901

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.0797 AC: 2794 AN: 35046 Hom.: 166 AF XY: 0.0781 AC XY: 1334 AN XY: 17086

African (AFR) AF: 0.417 AC: 236 AN: 566

American (AMR) AF: 0.0682 AC: 3 AN: 44

Ashkenazi Jewish (ASJ) AF: 0.0333 AC: 7 AN: 210

East Asian (EAS) AF: 0.131 AC: 22 AN: 168

South Asian (SAS) AF: 0.0559 AC: 37 AN: 662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AF: 0.0581 AC: 5 AN: 86

European-Non Finnish (NFE) AF: 0.0743 AC: 2389 AN: 32160

Other (OTH) AF: 0.0832 AC: 95 AN: 1142

GnomAD4 genome AF: 0.185 AC: 28148 AN: 151808 Hom.: 4111 Cov.: 32 AF XY: 0.181 AC XY: 13462 AN XY: 74194

African (AFR) AF: 0.416 AC: 17246 AN: 41424

American (AMR) AF: 0.136 AC: 2072 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.0504 AC: 175 AN: 3470

East Asian (EAS) AF: 0.156 AC: 804 AN: 5154

South Asian (SAS) AF: 0.0883 AC: 425 AN: 4812

European-Finnish (FIN) AF: 0.0801 AC: 845 AN: 10544

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0901 AC: 6115 AN: 67900

Other (OTH) AF: 0.148 AC: 311 AN: 2108

Alfa AF: 0.0760 Hom.: 159

Bravo AF: 0.200

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.54
DANN	Benign	0.37
PhyloP100		-0.17
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: rs7695870; hg19: chr4-158263776;