chr11-88535877-G-A

Variant names:

• chr11-88535877-G-A
• rs178244
• NM_001143831.3:c.2631-10473C>T

Variant summary

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

The NM_001143831.3(GRM5):​c.2631-10473C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,026 control chromosomes in the GnomAD database, including 25,164 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 0.56 (25164 hom., cov: 33)
• Consequence: GRM5 NM_001143831.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423
• Publications: 4 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM5	NM_001143831.3	c.2631-10473C>T		intron_variant	Intron 8 of 9	ENST00000305447.5	NP_001137303.1
GRM5	NM_000842.5	c.2631-26373C>T		intron_variant	Intron 8 of 8		NP_000833.1
GRM5	NM_001384268.1	c.2631-26373C>T		intron_variant	Intron 8 of 8		NP_001371197.1
GRM5	XM_011542792.2	c.2631-10473C>T		intron_variant	Intron 8 of 9		XP_011541094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM5	ENST00000305447.5	c.2631-10473C>T		intron_variant	Intron 8 of 9	1	NM_001143831.3	ENSP00000306138.4
GRM5	ENST00000305432.9	c.2631-26373C>T		intron_variant	Intron 7 of 7	1		ENSP00000305905.5
GRM5	ENST00000455756.6	c.2631-26373C>T		intron_variant	Intron 8 of 8	2		ENSP00000405690.2

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85697 AN: 151902 Hom.: 25118 Cov.: 33

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.375

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.564 AC: 85801 AN: 152026 Hom.: 25164 Cov.: 33 AF XY: 0.566 AC XY: 42022 AN XY: 74298

African (AFR) AF: 0.717 AC: 29747 AN: 41478

American (AMR) AF: 0.549 AC: 8383 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1499 AN: 3472

East Asian (EAS) AF: 0.696 AC: 3600 AN: 5176

South Asian (SAS) AF: 0.646 AC: 3118 AN: 4824

European-Finnish (FIN) AF: 0.491 AC: 5174 AN: 10542

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32546 AN: 67940

Other (OTH) AF: 0.538 AC: 1135 AN: 2108

Alfa AF: 0.497 Hom.: 32688

Bravo AF: 0.572

Asia WGS AF: 0.648 AC: 2246 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.29
DANN	Benign	0.45
PhyloP100		-0.42
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: rs178244; hg19: chr11-88269045;