7-86718721-A-G

Variant names:

• chr7-86718721-A-G
• rs2237547
• NM_000840.3:c.-140-46285A>G

Variant summary

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

The NM_000840.3(GRM3):​c.-140-46285A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,778 control chromosomes in the GnomAD database, including 14,828 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 0.40 (14828 hom., cov: 32)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545
• Publications: 3 publications found

Genes affected

GRM3 (HGNC:4595): (glutamate metabotropic receptor 3) 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. [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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM3	NM_000840.3	c.-140-46285A>G		intron_variant	Intron 1 of 5	ENST00000361669.7	NP_000831.2
GRM3	NM_001363522.2	c.-140-46285A>G		intron_variant	Intron 1 of 4		NP_001350451.1
GRM3	XM_047420268.1	c.-140-46285A>G		intron_variant	Intron 2 of 6		XP_047276224.1
GRM3	XM_017012073.3	c.-140-46285A>G		intron_variant	Intron 1 of 3		XP_016867562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM3	ENST00000361669.7	c.-140-46285A>G		intron_variant	Intron 1 of 5	1	NM_000840.3	ENSP00000355316.2

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60251 AN: 151660 Hom.: 14776 Cov.: 32

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.398 AC: 60359 AN: 151778 Hom.: 14828 Cov.: 32 AF XY: 0.392 AC XY: 29113 AN XY: 74216

African (AFR) AF: 0.703 AC: 29107 AN: 41398

American (AMR) AF: 0.285 AC: 4336 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1290 AN: 3468

East Asian (EAS) AF: 0.215 AC: 1104 AN: 5136

South Asian (SAS) AF: 0.254 AC: 1221 AN: 4816

European-Finnish (FIN) AF: 0.261 AC: 2762 AN: 10582

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19324 AN: 67886

Other (OTH) AF: 0.364 AC: 763 AN: 2098

Alfa AF: 0.302 Hom.: 12997

Bravo AF: 0.410

Asia WGS AF: 0.288 AC: 1003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.90
DANN	Benign	0.62
PhyloP100		-0.55
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: rs2237547; hg19: chr7-86348037;