rs2237554

Variant names:

• chr7-86749580-A-C
• rs2237554
• NM_000840.3:c.-140-15426A>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.-140-15426A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,944 control chromosomes in the GnomAD database, including 15,361 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 0.40 (15361 hom., cov: 32)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• 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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 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.-140-15426A>C		intron	N/A	NP_000831.2
	GRM3	NM_001363522.2		c.-140-15426A>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.-140-15426A>C		intron	N/A	ENSP00000355316.2	Q14832-1
	GRM3	ENST00000439827.1	TSL:1	c.-140-15426A>C		intron	N/A	ENSP00000398767.1	Q14832-2
	GRM3	ENST00000953115.1		c.-140-15426A>C		intron	N/A	ENSP00000623174.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61034 AN: 151826 Hom.: 15308 Cov.: 32

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.402 AC: 61141 AN: 151944 Hom.: 15361 Cov.: 32 AF XY: 0.396 AC XY: 29409 AN XY: 74272

African (AFR) AF: 0.718 AC: 29747 AN: 41418

American (AMR) AF: 0.291 AC: 4428 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1261 AN: 3468

East Asian (EAS) AF: 0.206 AC: 1064 AN: 5168

South Asian (SAS) AF: 0.259 AC: 1251 AN: 4826

European-Finnish (FIN) AF: 0.252 AC: 2671 AN: 10590

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19470 AN: 67918

Other (OTH) AF: 0.372 AC: 785 AN: 2112

Alfa AF: 0.333 Hom.: 5776

Bravo AF: 0.415

Asia WGS AF: 0.292 AC: 1015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.8
DANN	Benign	0.63
PhyloP100		-0.044
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: rs2237554; hg19: chr7-86378896;