rs178244

Positions:

• chr11-88535877-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	UniProt
GRM5	NM_001143831.3	c.2631-10473C>T		intron_variant		ENST00000305447.5
GRM5	NM_000842.5	c.2631-26373C>T		intron_variant
GRM5	NM_001384268.1	c.2631-26373C>T		intron_variant
GRM5	XM_011542792.2	c.2631-10473C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM5	ENST00000305447.5	c.2631-10473C>T		intron_variant		1	NM_001143831.3	A2
GRM5	ENST00000305432.9	c.2631-26373C>T		intron_variant		1		P2
GRM5	ENST00000455756.6	c.2631-26373C>T		intron_variant		2		P2

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

Gnomad4 AFR AF: 0.717

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.696

Gnomad4 SAS AF: 0.646

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.538

Alfa AF: 0.489 Hom.: 24933

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

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: rs178244; hg19: chr11-88269045;