9-137140083-T-C

Position:

• chr9-137140083-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007327.4(GRIN1):​c.258+339T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,132 control chromosomes in the GnomAD database, including 1,998 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 0.15 (1998 hom., cov: 33)
• Consequence: GRIN1 NM_007327.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN1	NM_007327.4	c.258+339T>C		intron_variant		ENST00000371561.8	NP_015566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN1	ENST00000371561.8	c.258+339T>C		intron_variant		1	NM_007327.4	ENSP00000360616.3

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23113 AN: 152012 Hom.: 1986 Cov.: 33

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.0969

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.152 AC: 23165 AN: 152132 Hom.: 1998 Cov.: 33 AF XY: 0.158 AC XY: 11737 AN XY: 74394

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.0969

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.167

Alfa AF: 0.0872 Hom.: 155

Bravo AF: 0.153

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.71

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: rs2301364; hg19: chr9-140034535; COSMIC: COSV59301627;