chr11-88508859-C-G

Variant names:

• chr11-88508859-C-G
• rs569668690
• NM_001143831.3:c.3372G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001143831.3(GRM5):​c.3372G>C​(p.Thr1124Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000817 in 1,577,438 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00059 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00084 (31 hom.)
• Consequence: GRM5 NM_001143831.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.26
• 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]

GRM5-AS1 (HGNC:40265): (GRM5 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 11-88508859-C-G is Benign according to our data. Variant chr11-88508859-C-G is described in ClinVar as [Benign]. Clinvar id is 788114.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 90 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM5	NM_001143831.3	c.3372G>C	p.Thr1124Thr	synonymous_variant	Exon 10 of 10	ENST00000305447.5	NP_001137303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM5	ENST00000305447.5	c.3372G>C	p.Thr1124Thr	synonymous_variant	Exon 10 of 10	1	NM_001143831.3	ENSP00000306138.4
GRM5	ENST00000305432.9	c.3276G>C	p.Thr1092Thr	synonymous_variant	Exon 8 of 8	1		ENSP00000305905.5
GRM5	ENST00000455756.6	c.3276G>C	p.Thr1092Thr	synonymous_variant	Exon 9 of 9	2		ENSP00000405690.2
GRM5-AS1	ENST00000526448.1	n.4284C>G		non_coding_transcript_exon_variant	Exon 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.000579 AC: 88 AN: 151932 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0173

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.00179 AC: 339 AN: 189406 AF XY: 0.00228

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000356

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00171

GnomAD4 exome AF: 0.000840 AC: 1198 AN: 1425396 Hom.: 31 Cov.: 34 AF XY: 0.00119 AC XY: 843 AN XY: 706654

African (AFR) AF: 0.0000960 AC: 3 AN: 31238

American (AMR) AF: 0.0000252 AC: 1 AN: 39652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 37000

South Asian (SAS) AF: 0.0137 AC: 1114 AN: 81254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50904

Middle Eastern (MID) AF: 0.000350 AC: 2 AN: 5712

European-Non Finnish (NFE) AF: 0.00000639 AC: 7 AN: 1095438

Other (OTH) AF: 0.00120 AC: 71 AN: 59018

GnomAD4 genome AF: 0.000592 AC: 90 AN: 152042 Hom.: 1 Cov.: 32 AF XY: 0.000901 AC XY: 67 AN XY: 74350

African (AFR) AF: 0.0000964 AC: 4 AN: 41514

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.0177 AC: 85 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67950

Other (OTH) AF: 0.000475 AC: 1 AN: 2104

Alfa AF: 0.000128 Hom.: 1

Bravo AF: 0.000117

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.55
DANN	Benign	0.83
PhyloP100		-6.3
Mutation Taster		=97/3	polymorphism

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: rs569668690; hg19: chr11-88242027;