rs162209

Variant names:

• chr3-7700210-G-A
• rs162209
• NM_000844.4:c.2698+19915G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-7700210-G-A
• chr3-7700210-G-C

Variant summary

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

The NM_000844.4(GRM7):​c.2698+19915G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,924 control chromosomes in the GnomAD database, including 17,243 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 0.46 (17243 hom., cov: 31)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• 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

ENSG00000270207 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.2698+19915G>A		intron_variant	Intron 9 of 9	ENST00000357716.9	NP_000835.1
GRM7	NM_181874.3	c.*21+13762G>A		intron_variant	Intron 10 of 10		NP_870989.1
GRM7	XM_017006272.2	c.*21+13762G>A		intron_variant	Intron 10 of 10		XP_016861761.1
GRM7	XM_017006273.2	c.2200+19915G>A		intron_variant	Intron 9 of 9		XP_016861762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.2698+19915G>A		intron_variant	Intron 9 of 9	1	NM_000844.4	ENSP00000350348.4

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70502 AN: 151806 Hom.: 17220 Cov.: 31

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.465 AC: 70570 AN: 151924 Hom.: 17243 Cov.: 31 AF XY: 0.474 AC XY: 35190 AN XY: 74246

African (AFR) AF: 0.555 AC: 22967 AN: 41404

American (AMR) AF: 0.513 AC: 7836 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1783 AN: 3470

East Asian (EAS) AF: 0.801 AC: 4111 AN: 5132

South Asian (SAS) AF: 0.570 AC: 2747 AN: 4818

European-Finnish (FIN) AF: 0.460 AC: 4863 AN: 10568

Middle Eastern (MID) AF: 0.531 AC: 154 AN: 290

European-Non Finnish (NFE) AF: 0.366 AC: 24855 AN: 67954

Other (OTH) AF: 0.477 AC: 1008 AN: 2114

Alfa AF: 0.409 Hom.: 42627

Bravo AF: 0.476

Asia WGS AF: 0.692 AC: 2405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.72
DANN	Benign	0.58
PhyloP100		0.064
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: rs162209; hg19: chr3-7741897;