rs342034

Variant names:

• chr3-6861914-A-G
• rs342034
• NM_000844.4:c.519+7A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-6861914-A-G
• chr3-6861914-A-C
• chr3-6861914-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000844.4(GRM7):​c.519+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.962 in 1,604,048 control chromosomes in the GnomAD database, including 742,208 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (71307 hom., cov: 32)
  • Exomes 𝑓: 0.96 (670901 hom.)
• Consequence: GRM7 NM_000844.4 splice_region, intron
• Scores: Splicing: ADA: 0.0001396
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.408
• Publications: 9 publications found

Genes affected

GRM7 (HGNC:4599): (glutamate metabotropic receptor 7) L-glutamate is the major excitatory neurotransmitter in the central nervous system, and it activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors that have been divided into three groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5, and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3, while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

GRM7 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 3-6861914-A-G is Benign according to our data. Variant chr3-6861914-A-G is described in ClinVar as Benign. ClinVar VariationId is 1164860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000844.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	NM_000844.4	MANE Select	c.519+7A>G		splice_region intron	N/A	NP_000835.1	Q14831-1
	GRM7	NM_181874.3		c.519+7A>G		splice_region intron	N/A	NP_870989.1	Q14831-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	ENST00000357716.9	TSL:1 MANE Select	c.519+7A>G		splice_region intron	N/A	ENSP00000350348.4	Q14831-1
	GRM7	ENST00000389336.8	TSL:1	c.519+7A>G		splice_region intron	N/A	ENSP00000373987.4	Q14831-5
	GRM7	ENST00000389335.7	TSL:1	n.519+7A>G		splice_region intron	N/A	ENSP00000373986.3	Q14831-4

Frequencies

GnomAD3 genomes AF: 0.968 AC: 147189 AN: 152070 Hom.: 71248 Cov.: 32

Gnomad AFR AF: 0.993

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.976

Gnomad ASJ AF: 0.921

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.993

Gnomad FIN AF: 0.952

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.953

Gnomad OTH AF: 0.967

GnomAD2 exomes AF: 0.968 AC: 234992 AN: 242858 AF XY: 0.968

Gnomad AFR exome AF: 0.994

Gnomad AMR exome AF: 0.983

Gnomad ASJ exome AF: 0.922

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.953

Gnomad NFE exome AF: 0.954

Gnomad OTH exome AF: 0.961

GnomAD4 exome AF: 0.961 AC: 1395579 AN: 1451860 Hom.: 670901 Cov.: 39 AF XY: 0.962 AC XY: 693075 AN XY: 720604

African (AFR) AF: 0.994 AC: 33090 AN: 33304

American (AMR) AF: 0.982 AC: 43556 AN: 44374

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 23714 AN: 25664

East Asian (EAS) AF: 1.00 AC: 39511 AN: 39512

South Asian (SAS) AF: 0.991 AC: 84619 AN: 85384

European-Finnish (FIN) AF: 0.952 AC: 50317 AN: 52840

Middle Eastern (MID) AF: 0.949 AC: 5430 AN: 5722

European-Non Finnish (NFE) AF: 0.957 AC: 1057673 AN: 1105122

Other (OTH) AF: 0.962 AC: 57669 AN: 59938

GnomAD4 genome AF: 0.968 AC: 147307 AN: 152188 Hom.: 71307 Cov.: 32 AF XY: 0.968 AC XY: 71998 AN XY: 74372

African (AFR) AF: 0.993 AC: 41269 AN: 41566

American (AMR) AF: 0.976 AC: 14935 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.921 AC: 3198 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5074 AN: 5076

South Asian (SAS) AF: 0.993 AC: 4785 AN: 4820

European-Finnish (FIN) AF: 0.952 AC: 10088 AN: 10602

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.953 AC: 64833 AN: 68026

Other (OTH) AF: 0.967 AC: 2042 AN: 2112

Alfa AF: 0.959 Hom.: 29067

Bravo AF: 0.970

Asia WGS AF: 0.992 AC: 3448 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Benign	0.78
PhyloP100		0.41
Mutation Taster		=58/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00014
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.010		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: rs342034; hg19: chr3-6903601;