Variant chr3-6861914-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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:2

Conservation

PhyloP100: 0.408

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM7	NM_000844.4 linkuse as main transcript	c.519+7A>G		splice_region_variant, intron_variant		ENST00000357716.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM7	ENST00000357716.9 linkuse as main transcript	c.519+7A>G		splice_region_variant, intron_variant		1	NM_000844.4	P1	Q14831-1

Frequencies

GnomAD3 genomes

AF:

0.968

AC:

147189

AN:

152070

Hom.:

71248

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.968

AC:

234992

AN:

242858

Hom.:

113756

AF XY:

0.968

AC XY:

127618

AN XY:

131900

show subpopulations

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 SAS exome

AF:

0.991

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.:

AF XY:

0.962

AC XY:

693075

AN XY:

720604

show subpopulations

Gnomad4 AFR exome

AF:

0.994

Gnomad4 AMR exome

AF:

0.982

Gnomad4 ASJ exome

AF:

0.924

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.991

Gnomad4 FIN exome

AF:

0.952

Gnomad4 NFE exome

AF:

0.957

Gnomad4 OTH exome

AF:

0.962

GnomAD4 genome

AF:

0.968

AC:

147307

AN:

152188

Hom.:

71307

Cov.:

AF XY:

0.968

AC XY:

71998

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.993

Gnomad4 AMR

AF:

0.976

Gnomad4 ASJ

AF:

0.921

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.993

Gnomad4 FIN

AF:

0.952

Gnomad4 NFE

AF:

0.953

Gnomad4 OTH

AF:

0.967

Alfa

AF:

0.959

Hom.:

29067

Bravo

AF:

0.970

Asia WGS

AF:

0.992

AC:

3448

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 08, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.78

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over