7-86702440-T-C

Variant names:

• chr7-86702440-T-C
• rs2189814
• NM_000840.3:c.-141+57568T>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.-141+57568T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,822 control chromosomes in the GnomAD database, including 7,794 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 0.28 (7794 hom., cov: 32)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.474
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM3	NM_000840.3	MANE Select	c.-141+57568T>C		intron	N/A	NP_000831.2
	GRM3	NM_001363522.2		c.-141+57568T>C		intron	N/A	NP_001350451.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM3	ENST00000361669.7	TSL:1 MANE Select	c.-141+57568T>C		intron	N/A	ENSP00000355316.2
	GRM3	ENST00000439827.1	TSL:1	c.-141+57568T>C		intron	N/A	ENSP00000398767.1
	GRM3	ENST00000953115.1		c.-141+57568T>C		intron	N/A	ENSP00000623174.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42325 AN: 151704 Hom.: 7787 Cov.: 32

Gnomad AFR AF: 0.0817

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.279 AC: 42332 AN: 151822 Hom.: 7794 Cov.: 32 AF XY: 0.289 AC XY: 21428 AN XY: 74188

African (AFR) AF: 0.0815 AC: 3379 AN: 41480

American (AMR) AF: 0.456 AC: 6917 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1091 AN: 3464

East Asian (EAS) AF: 0.712 AC: 3646 AN: 5122

South Asian (SAS) AF: 0.592 AC: 2853 AN: 4816

European-Finnish (FIN) AF: 0.277 AC: 2935 AN: 10596

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20517 AN: 67852

Other (OTH) AF: 0.312 AC: 658 AN: 2112

Alfa AF: 0.278 Hom.: 9934

Bravo AF: 0.284

Asia WGS AF: 0.559 AC: 1942 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.6
DANN	Benign	0.80
PhyloP100		0.47
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: rs2189814; hg19: chr7-86331756;