rs56763064

Variant names:

• chr7-86765277-G-A
• rs56763064
• NM_000840.3:c.132G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-86765277-G-A
• chr7-86765277-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000840.3(GRM3):​c.132G>A​(p.Leu44Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00473 in 1,613,730 control chromosomes in the GnomAD database, including 270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (147 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (123 hom.)
• Consequence: GRM3 NM_000840.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.421
• Publications: 4 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 7-86765277-G-A is Benign according to our data. Variant chr7-86765277-G-A is described in ClinVar as Benign. ClinVar VariationId is 768176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.421 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0786 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000840.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM3	NM_000840.3	MANE Select	c.132G>A	p.Leu44Leu	synonymous	Exon 2 of 6	NP_000831.2
	GRM3	NM_001363522.2		c.132G>A	p.Leu44Leu	synonymous	Exon 2 of 5	NP_001350451.1	Q14832-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM3	ENST00000361669.7	TSL:1 MANE Select	c.132G>A	p.Leu44Leu	synonymous	Exon 2 of 6	ENSP00000355316.2	Q14832-1
	GRM3	ENST00000439827.1	TSL:1	c.132G>A	p.Leu44Leu	synonymous	Exon 2 of 5	ENSP00000398767.1	Q14832-2
	GRM3	ENST00000953115.1		c.132G>A	p.Leu44Leu	synonymous	Exon 2 of 6	ENSP00000623174.1

Frequencies

GnomAD3 genomes AF: 0.0239 AC: 3629 AN: 152074 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.0808

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.000809

Gnomad OTH AF: 0.0249

GnomAD2 exomes AF: 0.00641 AC: 1605 AN: 250532 AF XY: 0.00461

Gnomad AFR exome AF: 0.0807

Gnomad AMR exome AF: 0.00482

Gnomad ASJ exome AF: 0.00288

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000619

Gnomad OTH exome AF: 0.00442

GnomAD4 exome AF: 0.00274 AC: 4000 AN: 1461538 Hom.: 123 Cov.: 31 AF XY: 0.00242 AC XY: 1756 AN XY: 727078

African (AFR) AF: 0.0792 AC: 2650 AN: 33462

American (AMR) AF: 0.00571 AC: 255 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00256 AC: 67 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86248

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53414

Middle Eastern (MID) AF: 0.00555 AC: 32 AN: 5762

European-Non Finnish (NFE) AF: 0.000502 AC: 558 AN: 1111788

Other (OTH) AF: 0.00702 AC: 424 AN: 60384

GnomAD4 genome AF: 0.0239 AC: 3641 AN: 152192 Hom.: 147 Cov.: 32 AF XY: 0.0234 AC XY: 1739 AN XY: 74426

African (AFR) AF: 0.0809 AC: 3359 AN: 41520

American (AMR) AF: 0.0102 AC: 155 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.000809 AC: 55 AN: 68002

Other (OTH) AF: 0.0246 AC: 52 AN: 2110

Alfa AF: 0.0110 Hom.: 59

Bravo AF: 0.0281

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.000983

EpiControl AF: 0.000771

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	4.2
DANN	Benign	0.74
PhyloP100		0.42
Mutation Taster		=93/7	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: rs56763064; hg19: chr7-86394593;