rs10765819

Variant names:

• chr11-88998060-G-A
• rs10765819
• NM_001143831.3:c.661+49152C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-88998060-G-A
• chr11-88998060-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.661+49152C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 149,588 control chromosomes in the GnomAD database, including 15,086 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 0.43 (15086 hom., cov: 26)
• Consequence: GRM5 NM_001143831.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.977
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.582 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.661+49152C>T		intron	N/A	NP_001137303.1	P41594-1
	GRM5	NM_000842.5		c.661+49152C>T		intron	N/A	NP_000833.1	P41594-2
	GRM5	NM_001384268.1		c.661+49152C>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.661+49152C>T		intron	N/A	ENSP00000306138.4	P41594-1
	GRM5	ENST00000305432.9	TSL:1	c.661+49152C>T		intron	N/A	ENSP00000305905.5	P41594-2
	GRM5	ENST00000393294.3	TSL:1	c.725+10975C>T		intron	N/A	ENSP00000376972.3	A8MT20

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64049 AN: 149476 Hom.: 15083 Cov.: 26

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.428 AC: 64058 AN: 149588 Hom.: 15086 Cov.: 26 AF XY: 0.429 AC XY: 31298 AN XY: 72898

African (AFR) AF: 0.215 AC: 8711 AN: 40516

American (AMR) AF: 0.504 AC: 7570 AN: 15014

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1825 AN: 3452

East Asian (EAS) AF: 0.519 AC: 2604 AN: 5018

South Asian (SAS) AF: 0.600 AC: 2813 AN: 4686

European-Finnish (FIN) AF: 0.420 AC: 4246 AN: 10106

Middle Eastern (MID) AF: 0.497 AC: 144 AN: 290

European-Non Finnish (NFE) AF: 0.512 AC: 34574 AN: 67530

Other (OTH) AF: 0.468 AC: 970 AN: 2074

Alfa AF: 0.498 Hom.: 65781

Bravo AF: 0.424

Asia WGS AF: 0.532 AC: 1851 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.4
DANN	Benign	0.42
PhyloP100		-0.98
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: rs10765819; hg19: chr11-88731228; COSMIC: COSV59602305;