rs62237228

Variant names:

• chr3-6860480-A-C
• rs62237228
• ENST00000448328.6:c.-106+31776A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-6860480-A-C
• chr3-6860480-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000448328.6(GRM7):​c.-106+31776A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,172 control chromosomes in the GnomAD database, including 1,586 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 0.12 (1586 hom., cov: 32)
• Consequence: GRM7 ENST00000448328.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000448328.6. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	ENST00000448328.6	TSL:4	c.-106+31776A>C		intron	N/A	ENSP00000393799.2
	GRM7	ENST00000443259.1	TSL:4	n.*29-23740A>C		intron	N/A	ENSP00000404161.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18539 AN: 152054 Hom.: 1588 Cov.: 32

Gnomad AFR AF: 0.0306

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0904

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0398

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.122 AC: 18532 AN: 152172 Hom.: 1586 Cov.: 32 AF XY: 0.121 AC XY: 9031 AN XY: 74380

African (AFR) AF: 0.0305 AC: 1269 AN: 41550

American (AMR) AF: 0.118 AC: 1807 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0904 AC: 314 AN: 3472

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5174

South Asian (SAS) AF: 0.0398 AC: 192 AN: 4820

European-Finnish (FIN) AF: 0.222 AC: 2345 AN: 10568

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12118 AN: 67986

Other (OTH) AF: 0.115 AC: 243 AN: 2114

Alfa AF: 0.154 Hom.: 403

Bravo AF: 0.110

Asia WGS AF: 0.0230 AC: 80 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.44
PhyloP100		-0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs62237228; hg19: chr3-6902167;