rs11146020

Variant names:

• chr9-137138632-G-C
• rs11146020
• ENST00000371560.5:c.-855G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 37 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=-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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN1	ENST00000371560.5	c.-855G>C		5_prime_UTR_variant	Exon 1 of 20	1		ENSP00000360615.3

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

African (AFR) AF: 0.00 AC: 0 AN: 82

American (AMR) AF: 0.188 AC: 18 AN: 96

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 7 AN: 108

East Asian (EAS) AF: 0.240 AC: 107 AN: 446

South Asian (SAS) AF: 0.0588 AC: 2 AN: 34

European-Finnish (FIN) AF: 0.112 AC: 46 AN: 410

Middle Eastern (MID) AF: 0.250 AC: 3 AN: 12

European-Non Finnish (NFE) AF: 0.0893 AC: 217 AN: 2430

Other (OTH) AF: 0.0659 AC: 12 AN: 182

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

African (AFR) AF: 0.0226 AC: 938 AN: 41556

American (AMR) AF: 0.157 AC: 2401 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0778 AC: 270 AN: 3472

East Asian (EAS) AF: 0.181 AC: 932 AN: 5142

South Asian (SAS) AF: 0.111 AC: 533 AN: 4822

European-Finnish (FIN) AF: 0.126 AC: 1333 AN: 10606

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0980 AC: 6666 AN: 68012

Other (OTH) AF: 0.110 AC: 233 AN: 2110

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
PhyloP100		0.076
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11146020; hg19: chr9-140033084;