11-88781854-A-G

Position:

• chr11-88781854-A-G

Variant summary

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

The NM_001143831.3(GRM5):​c.911+68052T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,054 control chromosomes in the GnomAD database, including 22,634 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 0.50 (22634 hom., cov: 32)
• Consequence: GRM5 NM_001143831.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM5	NM_001143831.3	c.911+68052T>C		intron_variant		ENST00000305447.5	NP_001137303.1
GRM5	NM_000842.5	c.911+68052T>C		intron_variant			NP_000833.1
GRM5	NM_001384268.1	c.911+68052T>C		intron_variant			NP_001371197.1
GRM5	XM_011542792.2	c.911+68052T>C		intron_variant			XP_011541094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM5	ENST00000305447.5	c.911+68052T>C		intron_variant		1	NM_001143831.3	ENSP00000306138	A2
GRM5	ENST00000305432.9	c.911+68052T>C		intron_variant		1		ENSP00000305905	P2
GRM5	ENST00000455756.6	c.911+68052T>C		intron_variant		2		ENSP00000405690	P2

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75404 AN: 151936 Hom.: 22638 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.496 AC: 75400 AN: 152054 Hom.: 22634 Cov.: 32 AF XY: 0.485 AC XY: 36074 AN XY: 74304

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.527

Alfa AF: 0.657 Hom.: 41912

Bravo AF: 0.474

Asia WGS AF: 0.264 AC: 919 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	13
DANN	Benign	0.69

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: rs7119749; hg19: chr11-88515022;