rs524874

Variant names:

• chr11-88979215-A-G
• rs524874
• NM_001143831.3:c.661+67997T>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.661+67997T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,006 control chromosomes in the GnomAD database, including 30,258 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 0.62 (30258 hom., cov: 31)
• Consequence: GRM5 NM_001143831.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 7 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 = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM5	NM_001143831.3	c.661+67997T>C		intron_variant	Intron 2 of 9	ENST00000305447.5	NP_001137303.1
GRM5	NM_000842.5	c.661+67997T>C		intron_variant	Intron 2 of 8		NP_000833.1
GRM5	NM_001384268.1	c.661+67997T>C		intron_variant	Intron 2 of 8		NP_001371197.1
GRM5	XM_011542792.2	c.661+67997T>C		intron_variant	Intron 2 of 9		XP_011541094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM5	ENST00000305447.5	c.661+67997T>C		intron_variant	Intron 2 of 9	1	NM_001143831.3	ENSP00000306138.4
GRM5	ENST00000305432.9	c.661+67997T>C		intron_variant	Intron 1 of 7	1		ENSP00000305905.5
GRM5	ENST00000455756.6	c.661+67997T>C		intron_variant	Intron 2 of 8	2		ENSP00000405690.2
GRM5	ENST00000449371.6	c.221+29820T>C		intron_variant	Intron 2 of 3	3		ENSP00000403724.2

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93396 AN: 151888 Hom.: 30212 Cov.: 31

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.615 AC: 93496 AN: 152006 Hom.: 30258 Cov.: 31 AF XY: 0.610 AC XY: 45288 AN XY: 74302

African (AFR) AF: 0.825 AC: 34224 AN: 41498

American (AMR) AF: 0.578 AC: 8823 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1906 AN: 3466

East Asian (EAS) AF: 0.537 AC: 2774 AN: 5166

South Asian (SAS) AF: 0.665 AC: 3205 AN: 4820

European-Finnish (FIN) AF: 0.421 AC: 4443 AN: 10548

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36061 AN: 67926

Other (OTH) AF: 0.610 AC: 1285 AN: 2108

Alfa AF: 0.570 Hom.: 3197

Bravo AF: 0.635

Asia WGS AF: 0.623 AC: 2167 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	0.29
DANN	Benign	0.57
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: rs524874; hg19: chr11-88712383;