rs1990040

Variant names:

• chr7-86683758-A-G
• rs1990040
• NM_000840.3:c.-141+38886A>G

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+38886A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,118 control chromosomes in the GnomAD database, including 8,506 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 0.29 (8506 hom., cov: 32)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM3	NM_000840.3	c.-141+38886A>G		intron_variant	Intron 1 of 5	ENST00000361669.7	NP_000831.2
GRM3	NM_001363522.2	c.-141+38886A>G		intron_variant	Intron 1 of 4		NP_001350451.1
GRM3	XM_047420268.1	c.-141+38886A>G		intron_variant	Intron 2 of 6		XP_047276224.1
GRM3	XM_017012073.3	c.-141+38886A>G		intron_variant	Intron 1 of 3		XP_016867562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM3	ENST00000361669.7	c.-141+38886A>G		intron_variant	Intron 1 of 5	1	NM_000840.3	ENSP00000355316.2
GRM3	ENST00000439827.1	c.-141+38886A>G		intron_variant	Intron 1 of 4	1		ENSP00000398767.1
GRM3	ENST00000454217.1	c.84+38886A>G		intron_variant	Intron 1 of 1	3		ENSP00000405427.1
GRM3	ENST00000421579.1	c.-141+38787A>G		intron_variant	Intron 1 of 1	4		ENSP00000390037.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44649 AN: 152000 Hom.: 8499 Cov.: 32

Gnomad AFR AF: 0.0845

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.294 AC: 44655 AN: 152118 Hom.: 8506 Cov.: 32 AF XY: 0.305 AC XY: 22647 AN XY: 74350

African (AFR) AF: 0.0843 AC: 3500 AN: 41528

American (AMR) AF: 0.465 AC: 7098 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1087 AN: 3468

East Asian (EAS) AF: 0.719 AC: 3703 AN: 5150

South Asian (SAS) AF: 0.598 AC: 2883 AN: 4822

European-Finnish (FIN) AF: 0.326 AC: 3454 AN: 10584

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.322 AC: 21911 AN: 67988

Other (OTH) AF: 0.323 AC: 680 AN: 2108

Alfa AF: 0.257 Hom.: 2939

Bravo AF: 0.295

Asia WGS AF: 0.563 AC: 1957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.79
PhyloP100		0.037
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: rs1990040; hg19: chr7-86313074;