rs3828472

Variant names:

• chr3-7146319-A-C
• rs3828472
• NM_000844.4:c.520-133A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-7146319-A-C
• chr3-7146319-A-G
• chr3-7146319-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.520-133A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 683,554 control chromosomes in the GnomAD database, including 25,612 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 0.24 (4901 hom., cov: 32)
  • Exomes 𝑓: 0.27 (20711 hom.)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.520-133A>C		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.520-133A>C		intron_variant	Intron 1 of 9	1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.520-133A>C		intron_variant	Intron 1 of 11	2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36794 AN: 152022 Hom.: 4905 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.272 AC: 144515 AN: 531414 Hom.: 20711 AF XY: 0.272 AC XY: 76381 AN XY: 281264

African (AFR) AF: 0.157 AC: 2329 AN: 14790

American (AMR) AF: 0.147 AC: 4181 AN: 28442

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 4782 AN: 15690

East Asian (EAS) AF: 0.149 AC: 4917 AN: 33060

South Asian (SAS) AF: 0.227 AC: 12262 AN: 53944

European-Finnish (FIN) AF: 0.312 AC: 12191 AN: 39048

Middle Eastern (MID) AF: 0.254 AC: 545 AN: 2148

European-Non Finnish (NFE) AF: 0.303 AC: 95505 AN: 315342

Other (OTH) AF: 0.270 AC: 7803 AN: 28950

GnomAD4 genome AF: 0.242 AC: 36797 AN: 152140 Hom.: 4901 Cov.: 32 AF XY: 0.241 AC XY: 17917 AN XY: 74338

African (AFR) AF: 0.153 AC: 6356 AN: 41532

American (AMR) AF: 0.178 AC: 2726 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3468

East Asian (EAS) AF: 0.178 AC: 919 AN: 5166

South Asian (SAS) AF: 0.230 AC: 1109 AN: 4824

European-Finnish (FIN) AF: 0.322 AC: 3405 AN: 10584

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20356 AN: 67962

Other (OTH) AF: 0.233 AC: 492 AN: 2114

Alfa AF: 0.279 Hom.: 25677

Bravo AF: 0.225

Asia WGS AF: 0.229 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.054
DANN	Benign	0.51
PhyloP100		-1.4
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: rs3828472; hg19: chr3-7188006;