chr3-7578695-C-T

Variant names:

• chr3-7578695-C-T
• rs7614915
• NM_000844.4:c.1789C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000844.4(GRM7):​c.1789C>T​(p.Leu597Leu) 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 1,613,472 control chromosomes in the GnomAD database, including 60,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4818 hom., cov: 32)
  • Exomes 𝑓: 0.27 (56031 hom.)
• Consequence: GRM7 NM_000844.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.971
• Publications: 15 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 3-7578695-C-T is Benign according to our data. Variant chr3-7578695-C-T is described in ClinVar as Benign. ClinVar VariationId is 1168983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.971 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000844.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	NM_000844.4	MANE Select	c.1789C>T	p.Leu597Leu	synonymous	Exon 8 of 10	NP_000835.1	Q14831-1
	GRM7	NM_181874.3		c.1789C>T	p.Leu597Leu	synonymous	Exon 8 of 11	NP_870989.1	Q14831-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	ENST00000357716.9	TSL:1 MANE Select	c.1789C>T	p.Leu597Leu	synonymous	Exon 8 of 10	ENSP00000350348.4	Q14831-1
	GRM7	ENST00000389336.8	TSL:1	c.1789C>T	p.Leu597Leu	synonymous	Exon 8 of 10	ENSP00000373987.4	Q14831-5
	GRM7	ENST00000389335.7	TSL:1	n.1789C>T		non_coding_transcript_exon	Exon 8 of 11	ENSP00000373986.3	Q14831-4

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34549 AN: 151912 Hom.: 4807 Cov.: 32

Gnomad AFR AF: 0.0833

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.192

GnomAD2 exomes AF: 0.257 AC: 64707 AN: 251334 AF XY: 0.254

Gnomad AFR exome AF: 0.0778

Gnomad AMR exome AF: 0.288

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: 393615 AN: 1461442 Hom.: 56031 Cov.: 35 AF XY: 0.267 AC XY: 193828 AN XY: 727018

African (AFR) AF: 0.0726 AC: 2431 AN: 33476

American (AMR) AF: 0.279 AC: 12498 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 6224 AN: 26136

East Asian (EAS) AF: 0.158 AC: 6286 AN: 39698

South Asian (SAS) AF: 0.179 AC: 15404 AN: 86250

European-Finnish (FIN) AF: 0.425 AC: 22721 AN: 53412

Middle Eastern (MID) AF: 0.127 AC: 730 AN: 5766

European-Non Finnish (NFE) AF: 0.281 AC: 312435 AN: 1111596

Other (OTH) AF: 0.247 AC: 14886 AN: 60388

GnomAD4 genome AF: 0.227 AC: 34579 AN: 152030 Hom.: 4818 Cov.: 32 AF XY: 0.234 AC XY: 17379 AN XY: 74302

African (AFR) AF: 0.0833 AC: 3455 AN: 41490

American (AMR) AF: 0.254 AC: 3883 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 777 AN: 3468

East Asian (EAS) AF: 0.155 AC: 796 AN: 5140

South Asian (SAS) AF: 0.169 AC: 815 AN: 4824

European-Finnish (FIN) AF: 0.447 AC: 4718 AN: 10556

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19443 AN: 67948

Other (OTH) AF: 0.191 AC: 402 AN: 2110

Alfa AF: 0.260 Hom.: 14953

Bravo AF: 0.208

Asia WGS AF: 0.172 AC: 599 AN: 3478

EpiCase AF: 0.258

EpiControl AF: 0.252

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.9
DANN	Benign	0.75
PhyloP100		0.97
Mutation Taster		=99/1	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: rs7614915; hg19: chr3-7620382; COSMIC: COSV63130165; COSMIC: COSV63130165;