3-7541371-A-G

Variant names:

• chr3-7541371-A-G
• rs779742
• NM_000844.4:c.1516-37051A>G

Variant summary

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

The NM_000844.4(GRM7):​c.1516-37051A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,938 control chromosomes in the GnomAD database, including 12,560 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 0.39 (12560 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427
• Publications: 5 publications found

Genes affected

GRM7 (HGNC:4599): (glutamate metabotropic receptor 7) L-glutamate is the major excitatory neurotransmitter in the central nervous system, and it 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 three 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. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

GRM7-AS1 (HGNC:40267): (GRM7 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000844.4. 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
	GRM7	NM_000844.4	MANE Select	c.1516-37051A>G		intron	N/A	NP_000835.1
	GRM7	NM_181874.3		c.1516-37051A>G		intron	N/A	NP_870989.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	ENST00000357716.9	TSL:1 MANE Select	c.1516-37051A>G		intron	N/A	ENSP00000350348.4
	GRM7	ENST00000389336.8	TSL:1	c.1516-37051A>G		intron	N/A	ENSP00000373987.4
	GRM7	ENST00000389335.7	TSL:1	n.1516-37051A>G		intron	N/A	ENSP00000373986.3

Frequencies

GnomAD3 genomes AF: 0.389 AC: 58990 AN: 151820 Hom.: 12567 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.388 AC: 58992 AN: 151938 Hom.: 12560 Cov.: 32 AF XY: 0.391 AC XY: 29042 AN XY: 74228

African (AFR) AF: 0.206 AC: 8547 AN: 41464

American (AMR) AF: 0.415 AC: 6332 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1287 AN: 3464

East Asian (EAS) AF: 0.546 AC: 2820 AN: 5162

South Asian (SAS) AF: 0.351 AC: 1689 AN: 4816

European-Finnish (FIN) AF: 0.515 AC: 5417 AN: 10518

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31513 AN: 67948

Other (OTH) AF: 0.402 AC: 847 AN: 2108

Alfa AF: 0.384 Hom.: 2200

Bravo AF: 0.377

Asia WGS AF: 0.429 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.9
DANN	Benign	0.24
PhyloP100		0.43
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: rs779742; hg19: chr3-7583058;