chr6-34061271-G-C

Position:

• chr6-34061271-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000841.4(GRM4):​c.872+622C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 152,006 control chromosomes in the GnomAD database, including 29,563 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 0.62 (29552 hom., cov: 31)
  • Exomes 𝑓: 0.66 (11 hom.)
• Consequence: GRM4 NM_000841.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

Genes affected

GRM4 (HGNC:4596): (glutamate metabotropic receptor 4) L-glutamate is the major excitatory neurotransmitter in the central nervous system and 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 3 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. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

GRM4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM4	NM_000841.4	c.872+622C>G		intron_variant		ENST00000538487.7	NP_000832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM4	ENST00000538487.7	c.872+622C>G		intron_variant		2	NM_000841.4	ENSP00000440556.1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94318 AN: 151838 Hom.: 29547 Cov.: 31

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.633

GnomAD4 exome AF: 0.660 AC: 33 AN: 50 Hom.: 11 Cov.: 0 AF XY: 0.611 AC XY: 22 AN XY: 36

Gnomad4 ASJ exome AF: 0.250

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.700

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.621 AC: 94368 AN: 151956 Hom.: 29552 Cov.: 31 AF XY: 0.618 AC XY: 45886 AN XY: 74260

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.628

Alfa AF: 0.490 Hom.: 1293

Bravo AF: 0.622

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.92
DANN	Benign	0.68

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: rs6901097; hg19: chr6-34029048;