7-86792916-T-C

Variant names:

• chr7-86792916-T-C
• rs2237562
• NM_000840.3:c.1324+5800T>C

Variant summary

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

The NM_000840.3(GRM3):​c.1324+5800T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 151,838 control chromosomes in the GnomAD database, including 13,812 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 0.39 (13812 hom., cov: 31)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• Publications: 13 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]

GRM3-AS1 (HGNC:40264): (GRM3 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM3	NM_000840.3	c.1324+5800T>C		intron_variant	Intron 3 of 5	ENST00000361669.7	NP_000831.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM3	ENST00000361669.7	c.1324+5800T>C		intron_variant	Intron 3 of 5	1	NM_000840.3	ENSP00000355316.2

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59257 AN: 151720 Hom.: 13788 Cov.: 31

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.391 AC: 59324 AN: 151838 Hom.: 13812 Cov.: 31 AF XY: 0.389 AC XY: 28850 AN XY: 74206

African (AFR) AF: 0.660 AC: 27324 AN: 41394

American (AMR) AF: 0.310 AC: 4723 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1262 AN: 3472

East Asian (EAS) AF: 0.200 AC: 1029 AN: 5150

South Asian (SAS) AF: 0.294 AC: 1415 AN: 4812

European-Finnish (FIN) AF: 0.304 AC: 3193 AN: 10520

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.282 AC: 19171 AN: 67922

Other (OTH) AF: 0.373 AC: 787 AN: 2112

Alfa AF: 0.310 Hom.: 32386

Bravo AF: 0.399

Asia WGS AF: 0.274 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.092
DANN	Benign	0.50
PhyloP100		-0.064
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: rs2237562; hg19: chr7-86422232;