3-7503834-C-T

Variant names:

• chr3-7503834-C-T
• rs1450097
• NM_000844.4:c.1515+42112C>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.1515+42112C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,010 control chromosomes in the GnomAD database, including 36,262 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 0.69 (36262 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.717
• Publications: 3 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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.1515+42112C>T		intron_variant	Intron 7 of 9	ENST00000357716.9	NP_000835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.1515+42112C>T		intron_variant	Intron 7 of 9	1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.1515+42112C>T		intron_variant	Intron 7 of 11	2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104186 AN: 151892 Hom.: 36195 Cov.: 32

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.686 AC: 104322 AN: 152010 Hom.: 36262 Cov.: 32 AF XY: 0.694 AC XY: 51559 AN XY: 74312

African (AFR) AF: 0.757 AC: 31403 AN: 41480

American (AMR) AF: 0.656 AC: 10009 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2176 AN: 3468

East Asian (EAS) AF: 0.799 AC: 4116 AN: 5150

South Asian (SAS) AF: 0.693 AC: 3342 AN: 4820

European-Finnish (FIN) AF: 0.773 AC: 8187 AN: 10596

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43080 AN: 67934

Other (OTH) AF: 0.644 AC: 1357 AN: 2108

Alfa AF: 0.671 Hom.: 5182

Bravo AF: 0.679

Asia WGS AF: 0.758 AC: 2634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	10
DANN	Benign	0.50
PhyloP100		0.72
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: rs1450097; hg19: chr3-7545521;