rs2299472

Variant names:

• chr7-126580415-C-A
• rs2299472
• NM_000845.3:c.1494+28947G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-126580415-C-A
• chr7-126580415-C-G

Variant summary

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

The NM_000845.3(GRM8):​c.1494+28947G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,002 control chromosomes in the GnomAD database, including 8,133 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 0.31 (8133 hom., cov: 32)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.447
• Publications: 8 publications found

Genes affected

GRM8 (HGNC:4600): (glutamate metabotropic receptor 8) L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000845.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM8	NM_000845.3	MANE Select	c.1494+28947G>T		intron	N/A	NP_000836.2
	GRM8	NM_001371086.1		c.1494+28947G>T		intron	N/A	NP_001358015.1
	GRM8	NM_001127323.1		c.1494+28947G>T		intron	N/A	NP_001120795.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM8	ENST00000339582.7	TSL:5 MANE Select	c.1494+28947G>T		intron	N/A	ENSP00000344173.2
	GRM8	ENST00000358373.8	TSL:1	c.1494+28947G>T		intron	N/A	ENSP00000351142.3
	GRM8	ENST00000341617.7	TSL:1	n.*59+28947G>T		intron	N/A	ENSP00000345747.3

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46944 AN: 151886 Hom.: 8134 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.309 AC: 46947 AN: 152002 Hom.: 8133 Cov.: 32 AF XY: 0.309 AC XY: 22983 AN XY: 74280

African (AFR) AF: 0.152 AC: 6285 AN: 41472

American (AMR) AF: 0.290 AC: 4425 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1216 AN: 3470

East Asian (EAS) AF: 0.438 AC: 2263 AN: 5172

South Asian (SAS) AF: 0.421 AC: 2026 AN: 4818

European-Finnish (FIN) AF: 0.335 AC: 3538 AN: 10568

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.385 AC: 26155 AN: 67926

Other (OTH) AF: 0.317 AC: 669 AN: 2108

Alfa AF: 0.348 Hom.: 3291

Bravo AF: 0.295

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.69
PhyloP100		-0.45
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: rs2299472; hg19: chr7-126220469;