NM_000840.3:c.-140-52876T>C

Variant names:

• chr7-86712130-T-C
• rs2189816
• NM_000840.3:c.-140-52876T>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.-140-52876T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0987 in 152,094 control chromosomes in the GnomAD database, including 962 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 0.099 (962 hom., cov: 32)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 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.-140-52876T>C		intron	N/A	NP_000831.2
	GRM3	NM_001363522.2		c.-140-52876T>C		intron	N/A	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.-140-52876T>C		intron	N/A	ENSP00000355316.2	Q14832-1
	GRM3	ENST00000439827.1	TSL:1	c.-140-52876T>C		intron	N/A	ENSP00000398767.1	Q14832-2
	GRM3	ENST00000953115.1		c.-140-52876T>C		intron	N/A	ENSP00000623174.1

Frequencies

GnomAD3 genomes AF: 0.0989 AC: 15026 AN: 151976 Hom.: 962 Cov.: 32

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0940

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.0987 AC: 15017 AN: 152094 Hom.: 962 Cov.: 32 AF XY: 0.0965 AC XY: 7174 AN XY: 74336

African (AFR) AF: 0.0262 AC: 1089 AN: 41554

American (AMR) AF: 0.0938 AC: 1430 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3472

East Asian (EAS) AF: 0.00175 AC: 9 AN: 5156

South Asian (SAS) AF: 0.107 AC: 515 AN: 4828

European-Finnish (FIN) AF: 0.120 AC: 1276 AN: 10596

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10056 AN: 67924

Other (OTH) AF: 0.106 AC: 224 AN: 2112

Alfa AF: 0.125 Hom.: 983

Bravo AF: 0.0937

Asia WGS AF: 0.0410 AC: 145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.84
PhyloP100		-0.46
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: rs2189816; hg19: chr7-86341446;