11-88810547-C-T

Variant names:

• chr11-88810547-C-T
• rs12787863
• NM_001143831.3:c.911+39359G>A

Variant summary

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

The NM_001143831.3(GRM5):​c.911+39359G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,898 control chromosomes in the GnomAD database, including 6,710 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 0.27 (6710 hom., cov: 32)
• Consequence: GRM5 NM_001143831.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.883
• Publications: 10 publications found

Genes affected

GRM5 (HGNC:4597): (glutamate metabotropic receptor 5) This gene encodes a member of the G-protein coupled receptor 3 protein family. The encoded protein is a metabatropic glutamate receptor, whose signaling activates a phosphatidylinositol-calcium second messenger system. This protein may be involved in the regulation of neural network activity and synaptic plasticity. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. A pseudogene of this gene has been defined on chromosome 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143831.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM5	NM_001143831.3	MANE Select	c.911+39359G>A		intron	N/A	NP_001137303.1
	GRM5	NM_000842.5		c.911+39359G>A		intron	N/A	NP_000833.1
	GRM5	NM_001384268.1		c.911+39359G>A		intron	N/A	NP_001371197.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM5	ENST00000305447.5	TSL:1 MANE Select	c.911+39359G>A		intron	N/A	ENSP00000306138.4
	GRM5	ENST00000305432.9	TSL:1	c.911+39359G>A		intron	N/A	ENSP00000305905.5
	GRM5	ENST00000455756.6	TSL:2	c.911+39359G>A		intron	N/A	ENSP00000405690.2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40271 AN: 151780 Hom.: 6713 Cov.: 32

Gnomad AFR AF: 0.0765

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.265 AC: 40259 AN: 151898 Hom.: 6710 Cov.: 32 AF XY: 0.263 AC XY: 19498 AN XY: 74252

African (AFR) AF: 0.0764 AC: 3168 AN: 41486

American (AMR) AF: 0.208 AC: 3179 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1255 AN: 3468

East Asian (EAS) AF: 0.232 AC: 1200 AN: 5166

South Asian (SAS) AF: 0.258 AC: 1242 AN: 4814

European-Finnish (FIN) AF: 0.379 AC: 3999 AN: 10542

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25454 AN: 67864

Other (OTH) AF: 0.245 AC: 517 AN: 2106

Alfa AF: 0.326 Hom.: 27795

Bravo AF: 0.240

Asia WGS AF: 0.195 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.51
PhyloP100		-0.88
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: rs12787863; hg19: chr11-88543715;