3-7561507-C-T

Variant names:

• chr3-7561507-C-T
• rs1965222
• NM_000844.4:c.1516-16915C>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.1516-16915C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 456,316 control chromosomes in the GnomAD database, including 3,098 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 0.12 (1229 hom., cov: 32)
  • Exomes 𝑓: 0.10 (1869 hom.)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114
• Publications: 3 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 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.1516-16915C>T		intron	N/A	NP_000835.1
	GRM7	NM_181874.3		c.1516-16915C>T		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.1516-16915C>T		intron	N/A	ENSP00000350348.4
	GRM7	ENST00000389336.8	TSL:1	c.1516-16915C>T		intron	N/A	ENSP00000373987.4
	GRM7	ENST00000389335.7	TSL:1	n.1516-16915C>T		intron	N/A	ENSP00000373986.3

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18629 AN: 151922 Hom.: 1229 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.0960

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.0684

Gnomad SAS AF: 0.0255

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.0878

GnomAD2 exomes AF: 0.0940 AC: 12618 AN: 134250 AF XY: 0.0895

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.0831

Gnomad ASJ exome AF: 0.0783

Gnomad EAS exome AF: 0.0747

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.0845

GnomAD4 exome AF: 0.100 AC: 30421 AN: 304276 Hom.: 1869 Cov.: 0 AF XY: 0.0928 AC XY: 16084 AN XY: 173254

African (AFR) AF: 0.134 AC: 1152 AN: 8618

American (AMR) AF: 0.0814 AC: 2220 AN: 27282

Ashkenazi Jewish (ASJ) AF: 0.0782 AC: 842 AN: 10768

East Asian (EAS) AF: 0.0704 AC: 648 AN: 9208

South Asian (SAS) AF: 0.0290 AC: 1734 AN: 59718

European-Finnish (FIN) AF: 0.162 AC: 2071 AN: 12784

Middle Eastern (MID) AF: 0.0349 AC: 97 AN: 2780

European-Non Finnish (NFE) AF: 0.128 AC: 20259 AN: 158884

Other (OTH) AF: 0.0982 AC: 1398 AN: 14234

GnomAD4 genome AF: 0.123 AC: 18631 AN: 152040 Hom.: 1229 Cov.: 32 AF XY: 0.122 AC XY: 9055 AN XY: 74360

African (AFR) AF: 0.135 AC: 5600 AN: 41478

American (AMR) AF: 0.0958 AC: 1464 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 234 AN: 3470

East Asian (EAS) AF: 0.0684 AC: 353 AN: 5162

South Asian (SAS) AF: 0.0255 AC: 123 AN: 4826

European-Finnish (FIN) AF: 0.171 AC: 1810 AN: 10582

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8719 AN: 67934

Other (OTH) AF: 0.0883 AC: 186 AN: 2106

Alfa AF: 0.119 Hom.: 3751

Bravo AF: 0.119

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.55
PhyloP100		-0.11
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: rs1965222; hg19: chr3-7603194;