7-86744059-A-C

Variant names:

• chr7-86744059-A-C
• rs2237552
• NM_000840.3:c.-140-20947A>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.-140-20947A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0391 in 152,158 control chromosomes in the GnomAD database, including 136 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 0.039 (136 hom., cov: 31)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.948
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM3	NM_000840.3	c.-140-20947A>C		intron_variant	Intron 1 of 5	ENST00000361669.7	NP_000831.2
GRM3	NM_001363522.2	c.-140-20947A>C		intron_variant	Intron 1 of 4		NP_001350451.1
GRM3	XM_047420268.1	c.-140-20947A>C		intron_variant	Intron 2 of 6		XP_047276224.1
GRM3	XM_017012073.3	c.-140-20947A>C		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.-140-20947A>C		intron_variant	Intron 1 of 5	1	NM_000840.3	ENSP00000355316.2

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5936 AN: 152040 Hom.: 134 Cov.: 31

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.0494

Gnomad SAS AF: 0.0485

Gnomad FIN AF: 0.0425

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0284

Gnomad OTH AF: 0.0273

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

GnomAD4 genome AF: 0.0391 AC: 5952 AN: 152158 Hom.: 136 Cov.: 31 AF XY: 0.0396 AC XY: 2948 AN XY: 74376

African (AFR) AF: 0.0613 AC: 2545 AN: 41524

American (AMR) AF: 0.0225 AC: 343 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3472

East Asian (EAS) AF: 0.0499 AC: 257 AN: 5150

South Asian (SAS) AF: 0.0490 AC: 236 AN: 4818

European-Finnish (FIN) AF: 0.0425 AC: 452 AN: 10626

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0284 AC: 1931 AN: 67988

Other (OTH) AF: 0.0270 AC: 57 AN: 2112

Alfa AF: 0.0305 Hom.: 120

Bravo AF: 0.0373

Asia WGS AF: 0.0620 AC: 215 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	7.7
DANN	Benign	0.68
PhyloP100		0.95
Mutation Taster		=100/0	polymorphism

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: rs2237552; hg19: chr7-86373375;