chr3-7157758-T-G

Variant names:

• chr3-7157758-T-G
• rs10510349
• NM_000844.4:c.736+11090T>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.736+11090T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 151,686 control chromosomes in the GnomAD database, including 746 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 0.063 (746 hom., cov: 31)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 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.736+11090T>G		intron	N/A	NP_000835.1
	GRM7	NM_181874.3		c.736+11090T>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.736+11090T>G		intron	N/A	ENSP00000350348.4
	GRM7	ENST00000389336.8	TSL:1	c.736+11090T>G		intron	N/A	ENSP00000373987.4
	GRM7	ENST00000389335.7	TSL:1	n.736+11090T>G		intron	N/A	ENSP00000373986.3

Frequencies

GnomAD3 genomes AF: 0.0624 AC: 9451 AN: 151572 Hom.: 740 Cov.: 31

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0630

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.0900

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.00341

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00775

Gnomad OTH AF: 0.0567

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

GnomAD4 genome AF: 0.0625 AC: 9481 AN: 151686 Hom.: 746 Cov.: 31 AF XY: 0.0617 AC XY: 4571 AN XY: 74112

African (AFR) AF: 0.174 AC: 7158 AN: 41246

American (AMR) AF: 0.0640 AC: 973 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3468

East Asian (EAS) AF: 0.0900 AC: 463 AN: 5142

South Asian (SAS) AF: 0.0333 AC: 160 AN: 4806

European-Finnish (FIN) AF: 0.00341 AC: 36 AN: 10552

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00776 AC: 527 AN: 67954

Other (OTH) AF: 0.0557 AC: 117 AN: 2102

Alfa AF: 0.0315 Hom.: 95

Bravo AF: 0.0738

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		2.1
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: rs10510349; hg19: chr3-7199445;