rs7788115

Variant names:

• chr7-86843015-A-T
• rs7788115
• NM_000840.3:c.2391+3110A>T

Variant summary

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

The NM_000840.3(GRM3):​c.2391+3110A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,042 control chromosomes in the GnomAD database, including 1,449 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 0.12 (1449 hom., cov: 32)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM3	NM_000840.3	c.2391+3110A>T		intron_variant	Intron 4 of 5	ENST00000361669.7	NP_000831.2
GRM3	NM_001363522.2	c.1325-7355A>T		intron_variant	Intron 3 of 4		NP_001350451.1
GRM3	XM_047420268.1	c.2391+3110A>T		intron_variant	Intron 5 of 6		XP_047276224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM3	ENST00000361669.7	c.2391+3110A>T		intron_variant	Intron 4 of 5	1	NM_000840.3	ENSP00000355316.2
GRM3	ENST00000439827.1	c.1325-7355A>T		intron_variant	Intron 3 of 4	1		ENSP00000398767.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18457 AN: 151924 Hom.: 1450 Cov.: 32

Gnomad AFR AF: 0.0300

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0613

Gnomad SAS AF: 0.0896

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.121 AC: 18448 AN: 152042 Hom.: 1449 Cov.: 32 AF XY: 0.121 AC XY: 9003 AN XY: 74332

African (AFR) AF: 0.0299 AC: 1242 AN: 41520

American (AMR) AF: 0.105 AC: 1603 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3470

East Asian (EAS) AF: 0.0611 AC: 316 AN: 5174

South Asian (SAS) AF: 0.0894 AC: 430 AN: 4808

European-Finnish (FIN) AF: 0.191 AC: 2018 AN: 10558

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11741 AN: 67940

Other (OTH) AF: 0.128 AC: 271 AN: 2110

Alfa AF: 0.162 Hom.: 310

Bravo AF: 0.110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.80
PhyloP100		-0.42
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: rs7788115; hg19: chr7-86472331;