11-88824823-A-G

Variant names:

• chr11-88824823-A-G
• rs10831496
• NM_001143831.3:c.911+25083T>C

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+25083T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 151,918 control chromosomes in the GnomAD database, including 21,480 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 0.49 (21480 hom., cov: 31)
• Consequence: GRM5 NM_001143831.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 46 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM5	NM_001143831.3	c.911+25083T>C		intron_variant	Intron 3 of 9	ENST00000305447.5	NP_001137303.1
GRM5	NM_000842.5	c.911+25083T>C		intron_variant	Intron 3 of 8		NP_000833.1
GRM5	NM_001384268.1	c.911+25083T>C		intron_variant	Intron 3 of 8		NP_001371197.1
GRM5	XM_011542792.2	c.911+25083T>C		intron_variant	Intron 3 of 9		XP_011541094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM5	ENST00000305447.5	c.911+25083T>C		intron_variant	Intron 3 of 9	1	NM_001143831.3	ENSP00000306138.4
GRM5	ENST00000305432.9	c.911+25083T>C		intron_variant	Intron 2 of 7	1		ENSP00000305905.5
GRM5	ENST00000455756.6	c.911+25083T>C		intron_variant	Intron 3 of 8	2		ENSP00000405690.2

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74281 AN: 151800 Hom.: 21426 Cov.: 31

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.490 AC: 74400 AN: 151918 Hom.: 21480 Cov.: 31 AF XY: 0.500 AC XY: 37154 AN XY: 74250

African (AFR) AF: 0.764 AC: 31642 AN: 41440

American (AMR) AF: 0.537 AC: 8198 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1014 AN: 3472

East Asian (EAS) AF: 0.758 AC: 3907 AN: 5154

South Asian (SAS) AF: 0.647 AC: 3111 AN: 4808

European-Finnish (FIN) AF: 0.413 AC: 4353 AN: 10540

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20608 AN: 67940

Other (OTH) AF: 0.464 AC: 977 AN: 2104

Alfa AF: 0.369 Hom.: 47923

Bravo AF: 0.510

Asia WGS AF: 0.735 AC: 2554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.035
DANN	Benign	0.34
PhyloP100		-1.3
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: rs10831496; hg19: chr11-88557991;