rs3864075

Variant names:

• chr3-7659884-G-A
• rs3864075
• NM_000844.4:c.2452-20165G>A

Variant summary

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

The NM_000844.4(GRM7):​c.2452-20165G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.964 in 152,252 control chromosomes in the GnomAD database, including 70,783 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 0.96 (70783 hom., cov: 31)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 4 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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000270207 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 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.2452-20165G>A		intron	N/A	NP_000835.1
	GRM7	NM_181874.3		c.2452-20165G>A		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.2452-20165G>A		intron	N/A	ENSP00000350348.4
	GRM7	ENST00000389336.8	TSL:1	c.2452-20165G>A		intron	N/A	ENSP00000373987.4
	GRM7	ENST00000389335.7	TSL:1	n.2452-20165G>A		intron	N/A	ENSP00000373986.3

Frequencies

GnomAD3 genomes AF: 0.964 AC: 146684 AN: 152134 Hom.: 70732 Cov.: 31

Gnomad AFR AF: 0.962

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.969

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.979

Gnomad FIN AF: 0.976

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.947

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

GnomAD4 genome AF: 0.964 AC: 146793 AN: 152252 Hom.: 70783 Cov.: 31 AF XY: 0.965 AC XY: 71858 AN XY: 74440

African (AFR) AF: 0.962 AC: 39973 AN: 41562

American (AMR) AF: 0.968 AC: 14816 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.885 AC: 3073 AN: 3472

East Asian (EAS) AF: 0.985 AC: 5071 AN: 5146

South Asian (SAS) AF: 0.979 AC: 4720 AN: 4820

European-Finnish (FIN) AF: 0.976 AC: 10356 AN: 10614

Middle Eastern (MID) AF: 0.921 AC: 269 AN: 292

European-Non Finnish (NFE) AF: 0.965 AC: 65647 AN: 68028

Other (OTH) AF: 0.948 AC: 1998 AN: 2108

Alfa AF: 0.961 Hom.: 14919

Bravo AF: 0.963

Asia WGS AF: 0.968 AC: 3365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.15
DANN	Benign	0.50
PhyloP100		-1.4
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: rs3864075; hg19: chr3-7701571;