Variant chr9-137145912-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_007327.4(GRIN1):c.570+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000743 in 1,586,810 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00083 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00073 ( 9 hom. )

Consequence

GRIN1
NM_007327.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.414

Variant links:

Genes affected

GRIN1 (HGNC:4584): (glutamate ionotropic receptor NMDA type subunit 1) The protein encoded by this gene is a critical subunit of N-methyl-D-aspartate receptors, members of the glutamate receptor channel superfamily which are heteromeric protein complexes with multiple subunits arranged to form a ligand-gated ion channel. These subunits play a key role in the plasticity of synapses, which is believed to underlie memory and learning. Cell-specific factors are thought to control expression of different isoforms, possibly contributing to the functional diversity of the subunits. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2008]

GRIN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 9-137145912-G-A is Benign according to our data. Variant chr9-137145912-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 388019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000828 (126/152214) while in subpopulation SAS AF= 0.00207 (10/4828). AF 95% confidence interval is 0.00112. There are 1 homozygotes in gnomad4. There are 57 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 9 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN1	NM_007327.4 linkuse as main transcript	c.570+10G>A		intron_variant		ENST00000371561.8	NP_015566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN1	ENST00000371561.8 linkuse as main transcript	c.570+10G>A		intron_variant		1	NM_007327.4	ENSP00000360616		Q05586-1

Frequencies

GnomAD3 genomes

AF:

0.000828

AC:

126

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.0242

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00166

AC:

330

AN:

199148

Hom.:

AF XY:

0.00182

AC XY:

197

AN XY:

108088

show subpopulations

Gnomad AFR exome

AF:

0.0000854

Gnomad AMR exome

AF:

0.0000340

Gnomad ASJ exome

AF:

0.0222

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00229

Gnomad FIN exome

AF:

0.0000594

Gnomad NFE exome

AF:

0.000570

Gnomad OTH exome

AF:

0.00332

GnomAD4 exome

AF:

0.000734

AC:

1053

AN:

1434596

Hom.:

Cov.:

AF XY:

0.000845

AC XY:

601

AN XY:

711560

show subpopulations

Gnomad4 AFR exome

AF:

0.0000303

Gnomad4 AMR exome

AF:

0.0000978

Gnomad4 ASJ exome

AF:

0.0194

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00218

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000201

Gnomad4 OTH exome

AF:

0.00201

GnomAD4 genome

AF:

0.000828

AC:

126

AN:

152214

Hom.:

Cov.:

AF XY:

0.000766

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.0242

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00384

Hom.:

Bravo

AF:

0.000835

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 11, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Intellectual disability, autosomal dominant 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 27, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.8

DANN

Benign

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

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