rs7627369

Positions:

• chr3-7654348-T-A

Variant summary

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

The NM_000844.4(GRM7):​c.2452-25701T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 152,210 control chromosomes in the GnomAD database, including 62 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 0.022 (62 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0225 (3423/152210) while in subpopulation AFR AF= 0.0333 (1384/41542). AF 95% confidence interval is 0.0319. There are 62 homozygotes in gnomad4. There are 1626 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 62 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM7	NM_000844.4	c.2452-25701T>A		intron_variant		ENST00000357716.9	NP_000835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.2452-25701T>A		intron_variant		1	NM_000844.4	ENSP00000350348	P1
	ENST00000652500.1	n.385-40085A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3415 AN: 152092 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0333

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0201

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.00830

Gnomad FIN AF: 0.00915

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0148

Gnomad OTH AF: 0.0388

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

GnomAD4 genome AF: 0.0225 AC: 3423 AN: 152210 Hom.: 62 Cov.: 32 AF XY: 0.0218 AC XY: 1626 AN XY: 74424

Gnomad4 AFR AF: 0.0333

Gnomad4 AMR AF: 0.0201

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.0140

Gnomad4 SAS AF: 0.00831

Gnomad4 FIN AF: 0.00915

Gnomad4 NFE AF: 0.0148

Gnomad4 OTH AF: 0.0384

Alfa AF: 0.0212 Hom.: 4

Bravo AF: 0.0240

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.1
DANN	Benign	0.67

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: rs7627369; hg19: chr3-7696035;