rs17726576

Positions:

• chr3-7740864-C-T

Variant summary

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

The NM_000844.4(GRM7):​c.*458C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 154,116 control chromosomes in the GnomAD database, including 19 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 0.015 (18 hom., cov: 32)
  • Exomes 𝑓: 0.017 (1 hom.)
• Consequence: GRM7 NM_000844.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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=-0.79).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0148 (2253/152246) while in subpopulation NFE AF= 0.0213 (1446/68020). AF 95% confidence interval is 0.0203. There are 18 homozygotes in gnomad4. There are 1032 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM7	NM_000844.4	c.*458C>T		3_prime_UTR_variant	10/10	ENST00000357716.9	NP_000835.1
GRM7	NM_181874.3	c.*529C>T		3_prime_UTR_variant	11/11		NP_870989.1
GRM7	XM_017006272.2	c.*529C>T		3_prime_UTR_variant	11/11		XP_016861761.1
GRM7	XM_017006273.2	c.*458C>T		3_prime_UTR_variant	10/10		XP_016861762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.*458C>T		3_prime_UTR_variant	10/10	1	NM_000844.4	ENSP00000350348	P1
	ENST00000652500.1	n.384+48973G>A		intron_variant, non_coding_transcript_variant
GRM7	ENST00000486284.5	c.*529C>T		3_prime_UTR_variant	11/11	5		ENSP00000417536
GRM7	ENST00000706913.1	c.*883C>T		3_prime_UTR_variant, NMD_transcript_variant	6/6			ENSP00000516622

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2254 AN: 152128 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.00422

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0145

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0213

Gnomad OTH AF: 0.0239

GnomAD4 exome AF: 0.0166 AC: 31 AN: 1870 Hom.: 1 Cov.: 0 AF XY: 0.0175 AC XY: 17 AN XY: 970

Gnomad4 AFR exome AF: 0.0125

Gnomad4 AMR exome AF: 0.0667

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0124

Gnomad4 NFE exome AF: 0.0191

Gnomad4 OTH exome AF: 0.0204

GnomAD4 genome AF: 0.0148 AC: 2253 AN: 152246 Hom.: 18 Cov.: 32 AF XY: 0.0139 AC XY: 1032 AN XY: 74428

Gnomad4 AFR AF: 0.00421

Gnomad4 AMR AF: 0.0145

Gnomad4 ASJ AF: 0.0369

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.0202

Gnomad4 NFE AF: 0.0213

Gnomad4 OTH AF: 0.0236

Alfa AF: 0.0175 Hom.: 7

Bravo AF: 0.0143

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	17
DANN	Benign	0.83

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: rs17726576; hg19: chr3-7782551;