chr6-34047988-C-T

Variant names:

• chr6-34047988-C-T
• rs4711374
• NM_000841.4:c.1169-7240G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000841.4(GRM4):​c.1169-7240G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,116 control chromosomes in the GnomAD database, including 5,565 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 0.25 (5565 hom., cov: 32)
• Consequence: GRM4 NM_000841.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000841.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM4	NM_000841.4	MANE Select	c.1169-7240G>A		intron	N/A	NP_000832.1	Q14833-1
	GRM4	NM_001256811.3		c.1028-7240G>A		intron	N/A	NP_001243740.1	B7ZLU9
	GRM4	NM_001256809.3		c.821-7240G>A		intron	N/A	NP_001243738.1	Q14833-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM4	ENST00000538487.7	TSL:2 MANE Select	c.1169-7240G>A		intron	N/A	ENSP00000440556.1	Q14833-1
	GRM4	ENST00000609278.1	TSL:1	n.*406-7240G>A		intron	N/A	ENSP00000477016.1	V9GYR3
	GRM4	ENST00000936006.1		c.1265-7240G>A		intron	N/A	ENSP00000606065.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38020 AN: 151998 Hom.: 5571 Cov.: 32

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.250 AC: 38015 AN: 152116 Hom.: 5565 Cov.: 32 AF XY: 0.247 AC XY: 18379 AN XY: 74362

African (AFR) AF: 0.401 AC: 16615 AN: 41478

American (AMR) AF: 0.224 AC: 3418 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 557 AN: 3470

East Asian (EAS) AF: 0.316 AC: 1635 AN: 5166

South Asian (SAS) AF: 0.245 AC: 1180 AN: 4816

European-Finnish (FIN) AF: 0.156 AC: 1653 AN: 10596

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12207 AN: 67994

Other (OTH) AF: 0.259 AC: 546 AN: 2106

Alfa AF: 0.203 Hom.: 13658

Bravo AF: 0.264

Asia WGS AF: 0.306 AC: 1064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.6
DANN	Benign	0.43
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4711374; hg19: chr6-34015765;