NM_001143831.3:c.1147+5718G>C

Variant names:

• chr11-88647450-C-G
• rs7396713
• NM_001143831.3:c.1147+5718G>C

Variant summary

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

The NM_001143831.3(GRM5):​c.1147+5718G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,774 control chromosomes in the GnomAD database, including 27,580 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 0.56 (27580 hom., cov: 31)
• Consequence: GRM5 NM_001143831.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM5	NM_001143831.3	c.1147+5718G>C		intron_variant	Intron 4 of 9	ENST00000305447.5	NP_001137303.1
GRM5	NM_000842.5	c.1147+5718G>C		intron_variant	Intron 4 of 8		NP_000833.1
GRM5	NM_001384268.1	c.1147+5718G>C		intron_variant	Intron 4 of 8		NP_001371197.1
GRM5	XM_011542792.2	c.1147+5718G>C		intron_variant	Intron 4 of 9		XP_011541094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM5	ENST00000305447.5	c.1147+5718G>C		intron_variant	Intron 4 of 9	1	NM_001143831.3	ENSP00000306138.4
GRM5	ENST00000305432.9	c.1147+5718G>C		intron_variant	Intron 3 of 7	1		ENSP00000305905.5
GRM5	ENST00000455756.6	c.1147+5718G>C		intron_variant	Intron 4 of 8	2		ENSP00000405690.2

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85123 AN: 151656 Hom.: 27579 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.561 AC: 85135 AN: 151774 Hom.: 27580 Cov.: 31 AF XY: 0.563 AC XY: 41755 AN XY: 74150

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.807

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.563

Alfa AF: 0.526 Hom.: 1878

Bravo AF: 0.527

Asia WGS AF: 0.613 AC: 2133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.72

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: rs7396713; hg19: chr11-88380618;