rs905646

Variant names:

• chr11-88620634-G-A
• rs905646
• NM_001143831.3:c.1148-15670C>T

Variant summary

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

The NM_001143831.3(GRM5):​c.1148-15670C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 152,050 control chromosomes in the GnomAD database, including 41,077 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 0.68 (41077 hom., cov: 32)
• Consequence: GRM5 NM_001143831.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221
• Publications: 10 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 (NFE) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM5	NM_001143831.3	c.1148-15670C>T		intron_variant	Intron 4 of 9	ENST00000305447.5	NP_001137303.1
GRM5	NM_000842.5	c.1148-15670C>T		intron_variant	Intron 4 of 8		NP_000833.1
GRM5	NM_001384268.1	c.1148-15670C>T		intron_variant	Intron 4 of 8		NP_001371197.1
GRM5	XM_011542792.2	c.1148-15670C>T		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.1148-15670C>T		intron_variant	Intron 4 of 9	1	NM_001143831.3	ENSP00000306138.4
GRM5	ENST00000305432.9	c.1148-15670C>T		intron_variant	Intron 3 of 7	1		ENSP00000305905.5
GRM5	ENST00000455756.6	c.1148-15670C>T		intron_variant	Intron 4 of 8	2		ENSP00000405690.2

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103052 AN: 151932 Hom.: 41088 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.719

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

GnomAD4 genome AF: 0.678 AC: 103046 AN: 152050 Hom.: 41077 Cov.: 32 AF XY: 0.678 AC XY: 50387 AN XY: 74340

African (AFR) AF: 0.234 AC: 9698 AN: 41412

American (AMR) AF: 0.685 AC: 10449 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3159 AN: 3472

East Asian (EAS) AF: 0.630 AC: 3256 AN: 5166

South Asian (SAS) AF: 0.869 AC: 4189 AN: 4822

European-Finnish (FIN) AF: 0.828 AC: 8782 AN: 10600

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.896 AC: 60953 AN: 67996

Other (OTH) AF: 0.712 AC: 1503 AN: 2112

Alfa AF: 0.828 Hom.: 161345

Bravo AF: 0.643

Asia WGS AF: 0.663 AC: 2306 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.1
DANN	Benign	0.37
PhyloP100		0.22
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: rs905646; hg19: chr11-88353802;