7-86696058-A-G

Position:

• chr7-86696058-A-G

Variant summary

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

The NM_000840.3(GRM3):​c.-141+51186A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 151,510 control chromosomes in the GnomAD database, including 37,603 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 0.70 (37603 hom., cov: 32)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM3	NM_000840.3	c.-141+51186A>G		intron_variant		ENST00000361669.7
GRM3	NM_001363522.2	c.-141+51186A>G		intron_variant
GRM3	XM_017012073.3	c.-141+51186A>G		intron_variant
GRM3	XM_047420268.1	c.-141+51186A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM3	ENST00000361669.7	c.-141+51186A>G		intron_variant		1	NM_000840.3	P1
GRM3	ENST00000439827.1	c.-141+51186A>G		intron_variant		1
GRM3	ENST00000421579.1	c.-141+51087A>G		intron_variant		4
GRM3	ENST00000454217.1	c.84+51186A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.700 AC: 105910 AN: 151390 Hom.: 37540 Cov.: 32

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.700 AC: 106031 AN: 151510 Hom.: 37603 Cov.: 32 AF XY: 0.703 AC XY: 51998 AN XY: 73990

Gnomad4 AFR AF: 0.772

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.874

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.694

Alfa AF: 0.603 Hom.: 3543

Bravo AF: 0.715

Asia WGS AF: 0.855 AC: 2969 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.14
DANN	Benign	0.53

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: rs724226; hg19: chr7-86325374;