NM_000844.4:c.519+18164C>T

Variant names:

• chr3-6880071-C-T
• rs17031835
• NM_000844.4:c.519+18164C>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.519+18164C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,158 control chromosomes in the GnomAD database, including 879 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 0.11 (879 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.327
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.121 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	NM_000844.4	MANE Select	c.519+18164C>T		intron	N/A	NP_000835.1
	GRM7	NM_181874.3		c.519+18164C>T		intron	N/A	NP_870989.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	ENST00000357716.9	TSL:1 MANE Select	c.519+18164C>T		intron	N/A	ENSP00000350348.4
	GRM7	ENST00000389336.8	TSL:1	c.519+18164C>T		intron	N/A	ENSP00000373987.4
	GRM7	ENST00000389335.7	TSL:1	n.519+18164C>T		intron	N/A	ENSP00000373986.3

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16063 AN: 152038 Hom.: 877 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0741

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0999

Gnomad FIN AF: 0.0834

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0876

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

GnomAD4 genome AF: 0.106 AC: 16083 AN: 152158 Hom.: 879 Cov.: 32 AF XY: 0.105 AC XY: 7781 AN XY: 74366

African (AFR) AF: 0.112 AC: 4656 AN: 41522

American (AMR) AF: 0.126 AC: 1920 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0741 AC: 257 AN: 3468

East Asian (EAS) AF: 0.106 AC: 547 AN: 5154

South Asian (SAS) AF: 0.0995 AC: 480 AN: 4822

European-Finnish (FIN) AF: 0.0834 AC: 884 AN: 10594

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7025 AN: 67992

Other (OTH) AF: 0.0862 AC: 182 AN: 2112

Alfa AF: 0.109 Hom.: 335

Bravo AF: 0.110

Asia WGS AF: 0.0980 AC: 341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.66
PhyloP100		0.33
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: rs17031835; hg19: chr3-6921758;