rs11146020

chr9-137138632-G-C

Variant summary

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

The ENST00000371560.5(GRIN1):c.-855G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 156,014 control chromosomes in the GnomAD database, including 830 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 0.088 (808 hom., cov: 32)
  • Exomes 𝑓: 0.11 (22 hom.)
• Consequence: GRIN1 ENST00000371560.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN1	ENST00000371560.5	c.-855G>C		5_prime_UTR_variant	1/20	1		P3

Frequencies

GnomAD3 genomes AF: 0.0880 AC: 13392 AN: 152098 Hom.: 803 Cov.: 32

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0980

Gnomad OTH AF: 0.111

GnomAD4 exome AF: 0.108 AC: 412 AN: 3800 Hom.: 22 Cov.: 0 AF XY: 0.107 AC XY: 207 AN XY: 1942

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.0648

Gnomad4 EAS exome AF: 0.240

Gnomad4 SAS exome AF: 0.0588

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.0893

Gnomad4 OTH exome AF: 0.0659

GnomAD4 genome AF: 0.0881 AC: 13410 AN: 152214 Hom.: 808 Cov.: 32 AF XY: 0.0920 AC XY: 6847 AN XY: 74402

Gnomad4 AFR AF: 0.0226

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.0778

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.0980

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0925 Hom.: 92

Bravo AF: 0.0885

Asia WGS AF: 0.157 AC: 545 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.8
Dann	Benign	0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11146020; hg19: chr9-140033084;