rs1874946

Variant names:

• chr11-88623734-C-T
• rs1874946
• NM_001143831.3:c.1148-18770G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143831.3(GRM5):​c.1148-18770G>A 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 151,930 control chromosomes in the GnomAD database, including 27,520 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 (27520 hom., cov: 31)
• Consequence: GRM5 NM_001143831.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM5	NM_001143831.3	c.1148-18770G>A		intron_variant	Intron 4 of 9	ENST00000305447.5	NP_001137303.1
GRM5	NM_000842.5	c.1148-18770G>A		intron_variant	Intron 4 of 8		NP_000833.1
GRM5	NM_001384268.1	c.1148-18770G>A		intron_variant	Intron 4 of 8		NP_001371197.1
GRM5	XM_011542792.2	c.1148-18770G>A		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.1148-18770G>A		intron_variant	Intron 4 of 9	1	NM_001143831.3	ENSP00000306138.4
GRM5	ENST00000305432.9	c.1148-18770G>A		intron_variant	Intron 3 of 7	1		ENSP00000305905.5
GRM5	ENST00000455756.6	c.1148-18770G>A		intron_variant	Intron 4 of 8	2		ENSP00000405690.2

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85208 AN: 151812 Hom.: 27520 Cov.: 31

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.561 AC: 85218 AN: 151930 Hom.: 27520 Cov.: 31 AF XY: 0.563 AC XY: 41803 AN XY: 74226

African (AFR) AF: 0.216 AC: 8960 AN: 41404

American (AMR) AF: 0.556 AC: 8472 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2334 AN: 3466

East Asian (EAS) AF: 0.592 AC: 3055 AN: 5162

South Asian (SAS) AF: 0.805 AC: 3880 AN: 4818

European-Finnish (FIN) AF: 0.725 AC: 7646 AN: 10544

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48816 AN: 67970

Other (OTH) AF: 0.560 AC: 1184 AN: 2114

Alfa AF: 0.679 Hom.: 18647

Bravo AF: 0.526

Asia WGS AF: 0.608 AC: 2115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.53
DANN	Benign	0.35
PhyloP100		-1.2
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: rs1874946; hg19: chr11-88356902;