rs1400166

Variant names:

• chr3-7176488-G-A
• rs1400166
• NM_000844.4:c.736+29820G>A

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+29820G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,848 control chromosomes in the GnomAD database, including 9,148 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 0.33 (9148 hom., cov: 31)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.872
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.736+29820G>A		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+29820G>A		intron_variant	Intron 2 of 9	1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.736+29820G>A		intron_variant	Intron 2 of 11	2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50438 AN: 151728 Hom.: 9128 Cov.: 31

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.333 AC: 50505 AN: 151848 Hom.: 9148 Cov.: 31 AF XY: 0.328 AC XY: 24317 AN XY: 74194

African (AFR) AF: 0.494 AC: 20451 AN: 41416

American (AMR) AF: 0.229 AC: 3485 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 618 AN: 3466

East Asian (EAS) AF: 0.216 AC: 1109 AN: 5142

South Asian (SAS) AF: 0.242 AC: 1166 AN: 4818

European-Finnish (FIN) AF: 0.319 AC: 3355 AN: 10510

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19444 AN: 67948

Other (OTH) AF: 0.280 AC: 591 AN: 2112

Alfa AF: 0.289 Hom.: 11471

Bravo AF: 0.333

Asia WGS AF: 0.302 AC: 1052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.8
DANN	Benign	0.66
PhyloP100		0.87
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: rs1400166; hg19: chr3-7218175;