11-88646164-G-T

Position:

• chr11-88646164-G-T

Variant summary

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

The NM_001143831.3(GRM5):​c.1147+7004C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 151,994 control chromosomes in the GnomAD database, including 41,715 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 0.69 (41715 hom., cov: 32)
• Consequence: GRM5 NM_001143831.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.825

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM5	NM_001143831.3	c.1147+7004C>A		intron_variant		ENST00000305447.5	NP_001137303.1
GRM5	NM_000842.5	c.1147+7004C>A		intron_variant			NP_000833.1
GRM5	NM_001384268.1	c.1147+7004C>A		intron_variant			NP_001371197.1
GRM5	XM_011542792.2	c.1147+7004C>A		intron_variant			XP_011541094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM5	ENST00000305447.5	c.1147+7004C>A		intron_variant		1	NM_001143831.3	ENSP00000306138.4
GRM5	ENST00000305432.9	c.1147+7004C>A		intron_variant		1		ENSP00000305905.5
GRM5	ENST00000455756.6	c.1147+7004C>A		intron_variant		2		ENSP00000405690.2

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104451 AN: 151876 Hom.: 41720 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.901

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.898

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.687 AC: 104459 AN: 151994 Hom.: 41715 Cov.: 32 AF XY: 0.687 AC XY: 51040 AN XY: 74292

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.912

Gnomad4 EAS AF: 0.681

Gnomad4 SAS AF: 0.891

Gnomad4 FIN AF: 0.828

Gnomad4 NFE AF: 0.898

Gnomad4 OTH AF: 0.718

Alfa AF: 0.863 Hom.: 71971

Bravo AF: 0.654

Asia WGS AF: 0.711 AC: 2473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.50

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: rs11020772; hg19: chr11-88379332;