3-7529549-C-T

Variant names:

• chr3-7529549-C-T
• rs1872393
• NM_000844.4:c.1516-48873C>T

Variant summary

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

The NM_000844.4(GRM7):​c.1516-48873C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,848 control chromosomes in the GnomAD database, including 12,658 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 (12658 hom., cov: 31)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.81
• Publications: 2 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.458 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.1516-48873C>T		intron	N/A	NP_000835.1
	GRM7	NM_181874.3		c.1516-48873C>T		intron	N/A	NP_870989.1
	GRM7-AS1	NR_046606.1		n.38+5698G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	ENST00000357716.9	TSL:1 MANE Select	c.1516-48873C>T		intron	N/A	ENSP00000350348.4
	GRM7	ENST00000389336.8	TSL:1	c.1516-48873C>T		intron	N/A	ENSP00000373987.4
	GRM7	ENST00000389335.7	TSL:1	n.1516-48873C>T		intron	N/A	ENSP00000373986.3

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60159 AN: 151730 Hom.: 12665 Cov.: 31

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.396 AC: 60164 AN: 151848 Hom.: 12658 Cov.: 31 AF XY: 0.397 AC XY: 29482 AN XY: 74174

African (AFR) AF: 0.250 AC: 10351 AN: 41438

American (AMR) AF: 0.419 AC: 6381 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1285 AN: 3468

East Asian (EAS) AF: 0.457 AC: 2348 AN: 5138

South Asian (SAS) AF: 0.342 AC: 1648 AN: 4812

European-Finnish (FIN) AF: 0.507 AC: 5356 AN: 10560

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31394 AN: 67904

Other (OTH) AF: 0.407 AC: 858 AN: 2106

Alfa AF: 0.406 Hom.: 1659

Bravo AF: 0.386

Asia WGS AF: 0.402 AC: 1397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.51
PhyloP100		-2.8
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: rs1872393; hg19: chr3-7571236;