rs917071

Variant names:

• chr7-86724465-C-T
• rs917071
• NM_000840.3:c.-140-40541C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000840.3(GRM3):​c.-140-40541C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,912 control chromosomes in the GnomAD database, including 15,081 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 (15081 hom., cov: 32)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM3	NM_000840.3	c.-140-40541C>T		intron_variant	Intron 1 of 5	ENST00000361669.7	NP_000831.2
GRM3	NM_001363522.2	c.-140-40541C>T		intron_variant	Intron 1 of 4		NP_001350451.1
GRM3	XM_047420268.1	c.-140-40541C>T		intron_variant	Intron 2 of 6		XP_047276224.1
GRM3	XM_017012073.3	c.-140-40541C>T		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.-140-40541C>T		intron_variant	Intron 1 of 5	1	NM_000840.3	ENSP00000355316.2

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60717 AN: 151794 Hom.: 15027 Cov.: 32

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.400 AC: 60828 AN: 151912 Hom.: 15081 Cov.: 32 AF XY: 0.395 AC XY: 29308 AN XY: 74254

African (AFR) AF: 0.709 AC: 29396 AN: 41452

American (AMR) AF: 0.287 AC: 4380 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1260 AN: 3468

East Asian (EAS) AF: 0.218 AC: 1126 AN: 5162

South Asian (SAS) AF: 0.252 AC: 1212 AN: 4806

European-Finnish (FIN) AF: 0.262 AC: 2761 AN: 10556

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19454 AN: 67918

Other (OTH) AF: 0.368 AC: 775 AN: 2104

Alfa AF: 0.344 Hom.: 15743

Bravo AF: 0.412

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	-0.91
CADD	Benign	1.0
DANN	Benign	0.60
PhyloP100		-0.20
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: rs917071; hg19: chr7-86353781;