rs993909

Variant names:

• chr3-7036620-A-G
• rs993909
• NM_000844.4:c.520-109832A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-7036620-A-G
• chr3-7036620-A-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.520-109832A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,748 control chromosomes in the GnomAD database, including 14,196 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 0.42 (14196 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.673
• 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 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.520-109832A>G		intron_variant	Intron 1 of 9	ENST00000357716.9	NP_000835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.520-109832A>G		intron_variant	Intron 1 of 9	1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.520-109832A>G		intron_variant	Intron 1 of 11	2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63350 AN: 151628 Hom.: 14207 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.418 AC: 63355 AN: 151748 Hom.: 14196 Cov.: 32 AF XY: 0.417 AC XY: 30859 AN XY: 74086

African (AFR) AF: 0.259 AC: 10740 AN: 41476

American (AMR) AF: 0.427 AC: 6512 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1566 AN: 3466

East Asian (EAS) AF: 0.461 AC: 2375 AN: 5156

South Asian (SAS) AF: 0.582 AC: 2805 AN: 4820

European-Finnish (FIN) AF: 0.391 AC: 4098 AN: 10474

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.499 AC: 33818 AN: 67804

Other (OTH) AF: 0.437 AC: 922 AN: 2110

Alfa AF: 0.317 Hom.: 920

Bravo AF: 0.411

Asia WGS AF: 0.528 AC: 1833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.22
PhyloP100		0.67
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: rs993909; hg19: chr3-7078307;