rs2169660

Variant names:

• chr11-88807016-G-A
• rs2169660
• NM_001143831.3:c.911+42890C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-88807016-G-A
• chr11-88807016-G-C
• chr11-88807016-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.911+42890C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 151,940 control chromosomes in the GnomAD database, including 18,227 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 0.46 (18227 hom., cov: 33)
• Consequence: GRM5 NM_001143831.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.951
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.736 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.911+42890C>T		intron	N/A	NP_001137303.1	P41594-1
	GRM5	NM_000842.5		c.911+42890C>T		intron	N/A	NP_000833.1	P41594-2
	GRM5	NM_001384268.1		c.911+42890C>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.911+42890C>T		intron	N/A	ENSP00000306138.4	P41594-1
	GRM5	ENST00000305432.9	TSL:1	c.911+42890C>T		intron	N/A	ENSP00000305905.5	P41594-2
	GRM5	ENST00000962224.1		c.911+42890C>T		intron	N/A	ENSP00000632283.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69587 AN: 151822 Hom.: 18183 Cov.: 33

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.459 AC: 69694 AN: 151940 Hom.: 18227 Cov.: 33 AF XY: 0.471 AC XY: 34939 AN XY: 74256

African (AFR) AF: 0.660 AC: 27368 AN: 41468

American (AMR) AF: 0.523 AC: 7992 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1010 AN: 3460

East Asian (EAS) AF: 0.756 AC: 3909 AN: 5174

South Asian (SAS) AF: 0.646 AC: 3113 AN: 4816

European-Finnish (FIN) AF: 0.413 AC: 4351 AN: 10546

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20423 AN: 67888

Other (OTH) AF: 0.444 AC: 937 AN: 2110

Alfa AF: 0.352 Hom.: 6050

Bravo AF: 0.475

Asia WGS AF: 0.726 AC: 2520 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.7
DANN	Benign	0.73
PhyloP100		0.95
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: rs2169660; hg19: chr11-88540184;