rs965170

Variant names:

• chr3-7172876-C-T
• rs965170
• NM_000844.4:c.736+26208C>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.736+26208C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,718 control chromosomes in the GnomAD database, including 4,495 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 0.24 (4495 hom., cov: 30)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.736+26208C>T		intron_variant	Intron 2 of 9	ENST00000357716.9	NP_000835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.736+26208C>T		intron_variant	Intron 2 of 9	1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.736+26208C>T		intron_variant	Intron 2 of 11	2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36261 AN: 151600 Hom.: 4491 Cov.: 30

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.239 AC: 36274 AN: 151718 Hom.: 4495 Cov.: 30 AF XY: 0.239 AC XY: 17730 AN XY: 74102

African (AFR) AF: 0.208 AC: 8592 AN: 41322

American (AMR) AF: 0.147 AC: 2238 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 757 AN: 3470

East Asian (EAS) AF: 0.174 AC: 892 AN: 5134

South Asian (SAS) AF: 0.248 AC: 1197 AN: 4818

European-Finnish (FIN) AF: 0.353 AC: 3707 AN: 10494

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.267 AC: 18097 AN: 67906

Other (OTH) AF: 0.216 AC: 456 AN: 2110

Alfa AF: 0.251 Hom.: 21174

Bravo AF: 0.219

Asia WGS AF: 0.232 AC: 808 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.35
PhyloP100		-0.088
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: rs965170; hg19: chr3-7214563;