rs1485174

Variant names:

• chr3-7579141-G-A
• rs1485174
• NM_000844.4:c.2235G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000844.4(GRM7):​c.2235G>A​(p.Gly745Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,612,422 control chromosomes in the GnomAD database, including 60,565 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4792 hom., cov: 32)
  • Exomes 𝑓: 0.27 (55773 hom.)
• Consequence: GRM7 NM_000844.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.142
• Publications: 18 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-7579141-G-A is Benign according to our data. Variant chr3-7579141-G-A is described in ClinVar as Benign. ClinVar VariationId is 1168984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.142 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.2235G>A	p.Gly745Gly	synonymous_variant	Exon 8 of 10	ENST00000357716.9	NP_000835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.2235G>A	p.Gly745Gly	synonymous_variant	Exon 8 of 10	1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.2235G>A		non_coding_transcript_exon_variant	Exon 8 of 12	2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34479 AN: 151842 Hom.: 4781 Cov.: 32

Gnomad AFR AF: 0.0832

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.192

GnomAD2 exomes AF: 0.258 AC: 64715 AN: 251158 AF XY: 0.254

Gnomad AFR exome AF: 0.0778

Gnomad AMR exome AF: 0.292

Gnomad ASJ exome AF: 0.240

Gnomad EAS exome AF: 0.154

Gnomad FIN exome AF: 0.440

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.256

GnomAD4 exome AF: 0.269 AC: 392259 AN: 1460462 Hom.: 55773 Cov.: 34 AF XY: 0.266 AC XY: 193161 AN XY: 726600

African (AFR) AF: 0.0722 AC: 2416 AN: 33454

American (AMR) AF: 0.282 AC: 12609 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 6224 AN: 26132

East Asian (EAS) AF: 0.159 AC: 6296 AN: 39694

South Asian (SAS) AF: 0.179 AC: 15398 AN: 86236

European-Finnish (FIN) AF: 0.425 AC: 22723 AN: 53418

Middle Eastern (MID) AF: 0.126 AC: 727 AN: 5764

European-Non Finnish (NFE) AF: 0.280 AC: 311010 AN: 1110686

Other (OTH) AF: 0.246 AC: 14856 AN: 60360

GnomAD4 genome AF: 0.227 AC: 34510 AN: 151960 Hom.: 4792 Cov.: 32 AF XY: 0.233 AC XY: 17337 AN XY: 74264

African (AFR) AF: 0.0832 AC: 3450 AN: 41456

American (AMR) AF: 0.252 AC: 3849 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 775 AN: 3468

East Asian (EAS) AF: 0.155 AC: 795 AN: 5136

South Asian (SAS) AF: 0.170 AC: 815 AN: 4806

European-Finnish (FIN) AF: 0.449 AC: 4739 AN: 10564

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.285 AC: 19390 AN: 67950

Other (OTH) AF: 0.191 AC: 403 AN: 2112

Alfa AF: 0.252 Hom.: 4019

Bravo AF: 0.208

Asia WGS AF: 0.173 AC: 600 AN: 3478

EpiCase AF: 0.256

EpiControl AF: 0.251

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.45
PhyloP100		0.14
Mutation Taster		=98/2	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: rs1485174; hg19: chr3-7620828; COSMIC: COSV63132810; COSMIC: COSV63132810;