11-88679283-A-G

Variant names:

• chr11-88679283-A-G
• rs6483362
• NM_001143831.3:c.912-25880T>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.912-25880T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 152,042 control chromosomes in the GnomAD database, including 57,175 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 0.86 (57175 hom., cov: 31)
• Consequence: GRM5 NM_001143831.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM5	NM_001143831.3	c.912-25880T>C		intron_variant	Intron 3 of 9	ENST00000305447.5	NP_001137303.1
GRM5	NM_000842.5	c.912-25880T>C		intron_variant	Intron 3 of 8		NP_000833.1
GRM5	NM_001384268.1	c.912-25880T>C		intron_variant	Intron 3 of 8		NP_001371197.1
GRM5	XM_011542792.2	c.912-25880T>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.912-25880T>C		intron_variant	Intron 3 of 9	1	NM_001143831.3	ENSP00000306138.4
GRM5	ENST00000305432.9	c.912-25880T>C		intron_variant	Intron 2 of 7	1		ENSP00000305905.5
GRM5	ENST00000455756.6	c.912-25880T>C		intron_variant	Intron 3 of 8	2		ENSP00000405690.2

Frequencies

GnomAD3 genomes AF: 0.863 AC: 131079 AN: 151924 Hom.: 57161 Cov.: 31

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.947

Gnomad AMR AF: 0.919

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.954

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.875

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

GnomAD4 genome AF: 0.863 AC: 131138 AN: 152042 Hom.: 57175 Cov.: 31 AF XY: 0.864 AC XY: 64210 AN XY: 74334

African (AFR) AF: 0.720 AC: 29817 AN: 41436

American (AMR) AF: 0.919 AC: 14033 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 3239 AN: 3472

East Asian (EAS) AF: 0.888 AC: 4593 AN: 5170

South Asian (SAS) AF: 0.954 AC: 4590 AN: 4812

European-Finnish (FIN) AF: 0.873 AC: 9244 AN: 10584

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.922 AC: 62659 AN: 67986

Other (OTH) AF: 0.869 AC: 1838 AN: 2114

Alfa AF: 0.910 Hom.: 99126

Bravo AF: 0.858

Asia WGS AF: 0.895 AC: 3111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.72
PhyloP100		-1.4
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: rs6483362; hg19: chr11-88412451;