rs13242038

chr7-86685104-C-T

Variant summary

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

The NM_000840.3(GRM3):c.-141+40232C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,074 control chromosomes in the GnomAD database, including 2,847 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 (2847 hom., cov: 32)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM3	NM_000840.3	c.-141+40232C>T		intron_variant		ENST00000361669.7
GRM3	NM_001363522.2	c.-141+40232C>T		intron_variant
GRM3	XM_017012073.3	c.-141+40232C>T		intron_variant
GRM3	XM_047420268.1	c.-141+40232C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM3	ENST00000361669.7	c.-141+40232C>T		intron_variant		1	NM_000840.3	P1
GRM3	ENST00000439827.1	c.-141+40232C>T		intron_variant		1
GRM3	ENST00000421579.1	c.-141+40133C>T		intron_variant		4
GRM3	ENST00000454217.1	c.84+40232C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29106 AN: 151956 Hom.: 2845 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.0675

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.192 AC: 29136 AN: 152074 Hom.: 2847 Cov.: 32 AF XY: 0.187 AC XY: 13916 AN XY: 74354

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.0673

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.182

Alfa AF: 0.203 Hom.: 409

Bravo AF: 0.191

Asia WGS AF: 0.130 AC: 450 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.4
Dann	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs13242038; hg19: chr7-86314420;