7-86743568-A-C

Position:

• chr7-86743568-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000840.3(GRM3):​c.-140-21438A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,018 control chromosomes in the GnomAD database, including 15,229 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 (15229 hom., cov: 32)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.927

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM3	NM_000840.3	c.-140-21438A>C		intron_variant		ENST00000361669.7	NP_000831.2
GRM3	NM_001363522.2	c.-140-21438A>C		intron_variant			NP_001350451.1
GRM3	XM_017012073.3	c.-140-21438A>C		intron_variant			XP_016867562.1
GRM3	XM_047420268.1	c.-140-21438A>C		intron_variant			XP_047276224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM3	ENST00000361669.7	c.-140-21438A>C		intron_variant		1	NM_000840.3	ENSP00000355316	P1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60856 AN: 151900 Hom.: 15176 Cov.: 32

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.379

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: 0.286

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.401 AC: 60964 AN: 152018 Hom.: 15229 Cov.: 32 AF XY: 0.395 AC XY: 29340 AN XY: 74320

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.371

Alfa AF: 0.281 Hom.: 7677

Bravo AF: 0.414

Asia WGS AF: 0.294 AC: 1022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.66
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs757656; hg19: chr7-86372884;