9-137143947-A-G

Position:

• chr9-137143947-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GRIN1	NM_007327.4	c.394-1779A>G		intron_variant		ENST00000371561.8	NP_015566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN1	ENST00000371561.8	c.394-1779A>G		intron_variant		1	NM_007327.4	ENSP00000360616

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

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.412

Alfa AF: 0.447 Hom.: 3748

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs28489906; hg19: chr9-140038399;