3-7740807-A-T

Position:

• chr3-7740807-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_000844.4(GRM7):​c.*401A>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0077 in 162,640 control chromosomes in the GnomAD database, including 10 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 0.0076 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0095 (1 hom.)
• Consequence: GRM7 NM_000844.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.01

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00757 (1151/152052) while in subpopulation SAS AF= 0.0256 (123/4796). AF 95% confidence interval is 0.022. There are 9 homozygotes in gnomad4. There are 596 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM7	NM_000844.4	c.*401A>T		3_prime_UTR_variant	10/10	ENST00000357716.9	NP_000835.1
GRM7	NM_181874.3	c.*472A>T		3_prime_UTR_variant	11/11		NP_870989.1
GRM7	XM_017006272.2	c.*472A>T		3_prime_UTR_variant	11/11		XP_016861761.1
GRM7	XM_017006273.2	c.*401A>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.*401A>T		3_prime_UTR_variant	10/10	1	NM_000844.4	ENSP00000350348	P1
	ENST00000652500.1	n.384+49030T>A		intron_variant, non_coding_transcript_variant
GRM7	ENST00000486284.5	c.*472A>T		3_prime_UTR_variant	11/11	5		ENSP00000417536
GRM7	ENST00000706913.1	c.*826A>T		3_prime_UTR_variant, NMD_transcript_variant	6/6			ENSP00000516622

Frequencies

GnomAD3 genomes AF: 0.00758 AC: 1152 AN: 151934 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00189

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.00427

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0258

Gnomad FIN AF: 0.0171

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00969

Gnomad OTH AF: 0.00960

GnomAD4 exome AF: 0.00954 AC: 101 AN: 10588 Hom.: 1 Cov.: 0 AF XY: 0.0102 AC XY: 56 AN XY: 5472

Gnomad4 AFR exome AF: 0.00204

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00448

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0795

Gnomad4 FIN exome AF: 0.0220

Gnomad4 NFE exome AF: 0.00875

Gnomad4 OTH exome AF: 0.0142

GnomAD4 genome AF: 0.00757 AC: 1151 AN: 152052 Hom.: 9 Cov.: 32 AF XY: 0.00802 AC XY: 596 AN XY: 74308

Gnomad4 AFR AF: 0.00188

Gnomad4 AMR AF: 0.00426

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0256

Gnomad4 FIN AF: 0.0171

Gnomad4 NFE AF: 0.00969

Gnomad4 OTH AF: 0.00950

Alfa AF: 0.00102 Hom.: 0

Bravo AF: 0.00581

Asia WGS AF: 0.00693 AC: 24 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
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: rs56173829; hg19: chr3-7782494;