rs7610073

Variant names:

• chr3-7258914-G-A
• rs7610073
• NM_000844.4:c.737-39770G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-7258914-G-A
• chr3-7258914-G-C
• chr3-7258914-G-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.737-39770G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,222 control chromosomes in the GnomAD database, including 48,784 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 0.79 (48784 hom., cov: 34)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.737-39770G>A		intron_variant	Intron 2 of 9	ENST00000357716.9	NP_000835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.737-39770G>A		intron_variant	Intron 2 of 9	1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.737-39770G>A		intron_variant	Intron 2 of 11	2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120896 AN: 152104 Hom.: 48775 Cov.: 34

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.834

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

GnomAD4 genome AF: 0.794 AC: 120931 AN: 152222 Hom.: 48784 Cov.: 34 AF XY: 0.800 AC XY: 59517 AN XY: 74422

African (AFR) AF: 0.647 AC: 26878 AN: 41514

American (AMR) AF: 0.886 AC: 13556 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.926 AC: 3215 AN: 3472

East Asian (EAS) AF: 0.974 AC: 5039 AN: 5176

South Asian (SAS) AF: 0.839 AC: 4053 AN: 4832

European-Finnish (FIN) AF: 0.829 AC: 8797 AN: 10608

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56597 AN: 68010

Other (OTH) AF: 0.828 AC: 1748 AN: 2112

Alfa AF: 0.815 Hom.: 79188

Bravo AF: 0.794

Asia WGS AF: 0.867 AC: 3015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.9
DANN	Benign	0.58
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7610073; hg19: chr3-7300601;