NM_007327.4:c.394-1779A>G

Variant names:

• chr9-137143947-A-G
• rs28489906
• NM_007327.4:c.394-1779A>G

Variant summary

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

The NM_007327.4(GRIN1):​c.394-1779A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,130 control chromosomes in the GnomAD database, including 13,497 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 0.40 (13497 hom., cov: 33)
• Consequence: GRIN1 NM_007327.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.946
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AR, AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, MODERATE Submitted by: G2P, Ambry Genetics
• developmental and epileptic encephalopathy 101

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN1	NM_007327.4	c.394-1779A>G		intron_variant	Intron 2 of 19	ENST00000371561.8	NP_015566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN1	ENST00000371561.8	c.394-1779A>G		intron_variant	Intron 2 of 19	1	NM_007327.4	ENSP00000360616.3

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61479 AN: 152012 Hom.: 13485 Cov.: 33

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.404 AC: 61521 AN: 152130 Hom.: 13497 Cov.: 33 AF XY: 0.408 AC XY: 30320 AN XY: 74382

African (AFR) AF: 0.246 AC: 10222 AN: 41518

American (AMR) AF: 0.469 AC: 7171 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1389 AN: 3472

East Asian (EAS) AF: 0.221 AC: 1140 AN: 5170

South Asian (SAS) AF: 0.351 AC: 1692 AN: 4822

European-Finnish (FIN) AF: 0.586 AC: 6208 AN: 10586

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.474 AC: 32202 AN: 67956

Other (OTH) AF: 0.412 AC: 870 AN: 2110

Alfa AF: 0.443 Hom.: 3767

Bravo AF: 0.387

Asia WGS AF: 0.298 AC: 1041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.99
DANN	Benign	0.32
PhyloP100		-0.95
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: rs28489906; hg19: chr9-140038399;