chr11-88780468-G-A

Variant names:

• chr11-88780468-G-A
• rs10765770
• NM_001143831.3:c.911+69438C>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.911+69438C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,004 control chromosomes in the GnomAD database, including 23,799 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 0.53 (23799 hom., cov: 32)
• Consequence: GRM5 NM_001143831.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.694 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM5	NM_001143831.3	MANE Select	c.911+69438C>T		intron	N/A	NP_001137303.1
	GRM5	NM_000842.5		c.911+69438C>T		intron	N/A	NP_000833.1
	GRM5	NM_001384268.1		c.911+69438C>T		intron	N/A	NP_001371197.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM5	ENST00000305447.5	TSL:1 MANE Select	c.911+69438C>T		intron	N/A	ENSP00000306138.4
	GRM5	ENST00000305432.9	TSL:1	c.911+69438C>T		intron	N/A	ENSP00000305905.5
	GRM5	ENST00000455756.6	TSL:2	c.911+69438C>T		intron	N/A	ENSP00000405690.2

Frequencies

GnomAD3 genomes AF: 0.527 AC: 79997 AN: 151886 Hom.: 23800 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.574

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.526 AC: 80002 AN: 152004 Hom.: 23799 Cov.: 32 AF XY: 0.516 AC XY: 38312 AN XY: 74278

African (AFR) AF: 0.278 AC: 11530 AN: 41452

American (AMR) AF: 0.467 AC: 7120 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2459 AN: 3468

East Asian (EAS) AF: 0.313 AC: 1615 AN: 5158

South Asian (SAS) AF: 0.365 AC: 1752 AN: 4806

European-Finnish (FIN) AF: 0.589 AC: 6233 AN: 10578

Middle Eastern (MID) AF: 0.576 AC: 167 AN: 290

European-Non Finnish (NFE) AF: 0.699 AC: 47522 AN: 67968

Other (OTH) AF: 0.548 AC: 1158 AN: 2114

Alfa AF: 0.593 Hom.: 3488

Bravo AF: 0.507

Asia WGS AF: 0.308 AC: 1073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.93
DANN	Benign	0.68
PhyloP100		-0.16
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: rs10765770; hg19: chr11-88513636;