rs904462

Variant names:

• chr11-88697756-G-A
• rs904462
• NM_001143831.3:c.912-44353C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-88697756-G-A
• chr11-88697756-G-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.912-44353C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,154 control chromosomes in the GnomAD database, including 46,657 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 0.74 (46657 hom., cov: 34)
• Consequence: GRM5 NM_001143831.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.934 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.912-44353C>T		intron	N/A	NP_001137303.1	P41594-1
	GRM5	NM_000842.5		c.912-44353C>T		intron	N/A	NP_000833.1	P41594-2
	GRM5	NM_001384268.1		c.912-44353C>T		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.912-44353C>T		intron	N/A	ENSP00000306138.4	P41594-1
	GRM5	ENST00000305432.9	TSL:1	c.912-44353C>T		intron	N/A	ENSP00000305905.5	P41594-2
	GRM5	ENST00000962224.1		c.912-44353C>T		intron	N/A	ENSP00000632283.1

Frequencies

GnomAD3 genomes AF: 0.737 AC: 112064 AN: 152036 Hom.: 46668 Cov.: 34

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.970

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.897

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.737 AC: 112070 AN: 152154 Hom.: 46657 Cov.: 34 AF XY: 0.737 AC XY: 54797 AN XY: 74372

African (AFR) AF: 0.326 AC: 13516 AN: 41458

American (AMR) AF: 0.754 AC: 11518 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.970 AC: 3368 AN: 3472

East Asian (EAS) AF: 0.628 AC: 3246 AN: 5170

South Asian (SAS) AF: 0.898 AC: 4333 AN: 4824

European-Finnish (FIN) AF: 0.880 AC: 9326 AN: 10602

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 63983 AN: 68028

Other (OTH) AF: 0.777 AC: 1643 AN: 2114

Alfa AF: 0.879 Hom.: 101865

Bravo AF: 0.705

Asia WGS AF: 0.705 AC: 2454 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.040
DANN	Benign	0.17
PhyloP100		-1.6
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: rs904462; hg19: chr11-88430924;