11-88718866-G-T

Variant names:

• chr11-88718866-G-T
• rs1993842
• NM_001143831.3:c.912-65463C>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.912-65463C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 151,850 control chromosomes in the GnomAD database, including 54,895 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 0.83 (54895 hom., cov: 32)
• Consequence: GRM5 NM_001143831.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.964 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM5	NM_001143831.3	MANE Select	c.912-65463C>A		intron	N/A	NP_001137303.1	P41594-1
	GRM5	NM_000842.5		c.912-65463C>A		intron	N/A	NP_000833.1	P41594-2
	GRM5	NM_001384268.1		c.912-65463C>A		intron	N/A	NP_001371197.1	P41594-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM5	ENST00000305447.5	TSL:1 MANE Select	c.912-65463C>A		intron	N/A	ENSP00000306138.4	P41594-1
	GRM5	ENST00000305432.9	TSL:1	c.912-65463C>A		intron	N/A	ENSP00000305905.5	P41594-2
	GRM5	ENST00000962224.1		c.912-65463C>A		intron	N/A	ENSP00000632283.1

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126263 AN: 151732 Hom.: 54896 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.957

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.993

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.970

Gnomad OTH AF: 0.868

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

GnomAD4 genome AF: 0.832 AC: 126289 AN: 151850 Hom.: 54895 Cov.: 32 AF XY: 0.831 AC XY: 61718 AN XY: 74234

African (AFR) AF: 0.560 AC: 23176 AN: 41384

American (AMR) AF: 0.794 AC: 12057 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.993 AC: 3442 AN: 3468

East Asian (EAS) AF: 0.819 AC: 4206 AN: 5136

South Asian (SAS) AF: 0.959 AC: 4630 AN: 4830

European-Finnish (FIN) AF: 0.937 AC: 9938 AN: 10610

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.970 AC: 65861 AN: 67912

Other (OTH) AF: 0.866 AC: 1830 AN: 2112

Alfa AF: 0.928 Hom.: 271648

Bravo AF: 0.807

Asia WGS AF: 0.842 AC: 2929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.28
DANN	Benign	0.75
PhyloP100		-1.1
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: rs1993842; hg19: chr11-88452034;