rs12275483

Positions:

• chr11-89003956-C-A
• chr11-89003956-C-G
• chr11-89003956-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143831.3(GRM5):​c.661+43256G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0639 in 152,038 control chromosomes in the GnomAD database, including 1,022 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 0.064 (1022 hom., cov: 32)
• Consequence: GRM5 NM_001143831.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.585

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

Verdict is Benign. Variant got -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 = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM5	NM_001143831.3	c.661+43256G>T		intron_variant		ENST00000305447.5	NP_001137303.1
GRM5	NM_000842.5	c.661+43256G>T		intron_variant			NP_000833.1
GRM5	NM_001384268.1	c.661+43256G>T		intron_variant			NP_001371197.1
GRM5	XM_011542792.2	c.661+43256G>T		intron_variant			XP_011541094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM5	ENST00000305447.5	c.661+43256G>T		intron_variant		1	NM_001143831.3	ENSP00000306138	A2

Frequencies

GnomAD3 genomes AF: 0.0638 AC: 9693 AN: 151922 Hom.: 1020 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0221

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.0168

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00223

Gnomad OTH AF: 0.0431

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

GnomAD4 genome AF: 0.0639 AC: 9717 AN: 152038 Hom.: 1022 Cov.: 32 AF XY: 0.0625 AC XY: 4645 AN XY: 74334

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.0220

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.0170

Gnomad4 SAS AF: 0.0141

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.00224

Gnomad4 OTH AF: 0.0427

Alfa AF: 0.00975 Hom.: 18

Bravo AF: 0.0720

Asia WGS AF: 0.0380 AC: 131 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	0.53
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs12275483; hg19: chr11-88737124;