rs10510365

Variant names:

• chr3-7343681-T-G
• rs10510365
• NM_000844.4:c.1033+37029T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000844.4(GRM7):​c.1033+37029T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00941 in 152,252 control chromosomes in the GnomAD database, including 12 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 0.0094 (12 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00941 (1432/152252) while in subpopulation AMR AF= 0.027 (412/15254). AF 95% confidence interval is 0.0249. There are 12 homozygotes in gnomad4. There are 713 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.1033+37029T>G		intron_variant	Intron 4 of 9	ENST00000357716.9	NP_000835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.1033+37029T>G		intron_variant	Intron 4 of 9	1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.1033+37029T>G		intron_variant	Intron 4 of 11	2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.00940 AC: 1430 AN: 152134 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00246

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0270

Gnomad ASJ AF: 0.0204

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0103

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0192

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

GnomAD4 genome AF: 0.00941 AC: 1432 AN: 152252 Hom.: 12 Cov.: 32 AF XY: 0.00958 AC XY: 713 AN XY: 74436

Gnomad4 AFR AF: 0.00245

Gnomad4 AMR AF: 0.0270

Gnomad4 ASJ AF: 0.0204

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0103

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.00884 Hom.: 2

Bravo AF: 0.0111

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs10510365; hg19: chr3-7385368;