7-86844997-T-C

Variant names:

• chr7-86844997-T-C
• rs1989796
• NM_000840.3:c.2391+5092T>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.2391+5092T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 151,908 control chromosomes in the GnomAD database, including 34,295 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 0.65 (34295 hom., cov: 31)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.976
• Publications: 12 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM3	NM_000840.3	c.2391+5092T>C		intron_variant	Intron 4 of 5	ENST00000361669.7	NP_000831.2
GRM3	NM_001363522.2	c.1325-5373T>C		intron_variant	Intron 3 of 4		NP_001350451.1
GRM3	XM_047420268.1	c.2391+5092T>C		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+5092T>C		intron_variant	Intron 4 of 5	1	NM_000840.3	ENSP00000355316.2
GRM3	ENST00000439827.1	c.1325-5373T>C		intron_variant	Intron 3 of 4	1		ENSP00000398767.1

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97968 AN: 151790 Hom.: 34240 Cov.: 31

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.646 AC: 98079 AN: 151908 Hom.: 34295 Cov.: 31 AF XY: 0.637 AC XY: 47269 AN XY: 74234

African (AFR) AF: 0.908 AC: 37662 AN: 41472

American (AMR) AF: 0.484 AC: 7383 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1779 AN: 3462

East Asian (EAS) AF: 0.245 AC: 1259 AN: 5144

South Asian (SAS) AF: 0.322 AC: 1551 AN: 4822

European-Finnish (FIN) AF: 0.630 AC: 6641 AN: 10542

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39904 AN: 67896

Other (OTH) AF: 0.601 AC: 1266 AN: 2106

Alfa AF: 0.791 Hom.: 10442

Bravo AF: 0.647

Asia WGS AF: 0.362 AC: 1261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.68
PhyloP100		-0.98
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: rs1989796; hg19: chr7-86474313;