rs162724

Variant names:

• chr3-7727595-T-C
• rs162724
• NM_000844.4:c.2699-12762T>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.2699-12762T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 151,986 control chromosomes in the GnomAD database, including 6,338 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 0.25 (6338 hom., cov: 31)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.2699-12762T>C		intron_variant	Intron 9 of 9	ENST00000357716.9	NP_000835.1
GRM7	NM_181874.3	c.*22-12762T>C		intron_variant	Intron 10 of 10		NP_870989.1
GRM7	XM_017006272.2	c.*22-12762T>C		intron_variant	Intron 10 of 10		XP_016861761.1
GRM7	XM_017006273.2	c.2201-12762T>C		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.2699-12762T>C		intron_variant	Intron 9 of 9	1	NM_000844.4	ENSP00000350348.4

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38659 AN: 151868 Hom.: 6312 Cov.: 31

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0774

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.255 AC: 38735 AN: 151986 Hom.: 6338 Cov.: 31 AF XY: 0.254 AC XY: 18884 AN XY: 74284

African (AFR) AF: 0.462 AC: 19125 AN: 41400

American (AMR) AF: 0.185 AC: 2827 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 556 AN: 3470

East Asian (EAS) AF: 0.0774 AC: 401 AN: 5180

South Asian (SAS) AF: 0.160 AC: 770 AN: 4816

European-Finnish (FIN) AF: 0.268 AC: 2831 AN: 10544

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11745 AN: 67974

Other (OTH) AF: 0.196 AC: 413 AN: 2102

Alfa AF: 0.191 Hom.: 3848

Bravo AF: 0.258

Asia WGS AF: 0.115 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.60
PhyloP100		0.29
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: rs162724; hg19: chr3-7769282;