rs202160831

chr9-137139762-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_007327.4(GRIN1):c.258+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,597,266 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (2 hom.)
• Consequence: GRIN1 NM_007327.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.631

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 9-137139762-C-T is Benign according to our data. Variant chr9-137139762-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 384370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00127 (193/152236) while in subpopulation NFE AF= 0.00175 (119/68014). AF 95% confidence interval is 0.00149. There are 0 homozygotes in gnomad4. There are 93 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN1	NM_007327.4	c.258+18C>T		intron_variant		ENST00000371561.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN1	ENST00000371561.8	c.258+18C>T		intron_variant		1	NM_007327.4

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 193 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00480

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00175

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00144 AC: 356 AN: 247846 Hom.: 0 AF XY: 0.00150 AC XY: 202 AN XY: 134576

Gnomad AFR exome AF: 0.000310

Gnomad AMR exome AF: 0.000926

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.00101

Gnomad FIN exome AF: 0.00394

Gnomad NFE exome AF: 0.00178

Gnomad OTH exome AF: 0.000819

GnomAD4 exome AF: 0.00170 AC: 2450 AN: 1445030 Hom.: 2 Cov.: 28 AF XY: 0.00170 AC XY: 1227 AN XY: 719678

Gnomad4 AFR exome AF: 0.000271

Gnomad4 AMR exome AF: 0.00101

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000978

Gnomad4 FIN exome AF: 0.00395

Gnomad4 NFE exome AF: 0.00184

Gnomad4 OTH exome AF: 0.00119

GnomAD4 genome AF: 0.00127 AC: 193 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.00125 AC XY: 93 AN XY: 74430

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00480

Gnomad4 NFE AF: 0.00175

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00151 Hom.: 0

Bravo AF: 0.000880

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 17, 2017

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

May 11, 2017

- -

Intellectual disability, autosomal dominant 8 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	9.4
Dann	Benign	0.91

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: rs202160831; hg19: chr9-140034214;