rs201818201

Variant names:

• chr9-137156690-A-C
• rs201818201
• NM_007327.4:c.693A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-137156690-A-C
• chr9-137156690-A-G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_007327.4(GRIN1):​c.693A>C​(p.Val231Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000795 in 1,599,020 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V231V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00051 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00083 (1 hom.)
• Consequence: GRIN1 NM_007327.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.26
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae), 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: Ambry Genetics, G2P
• 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

LOC105376328 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 9-137156690-A-C is Benign according to our data. Variant chr9-137156690-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 385654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.26 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000512 (78/152328) while in subpopulation SAS AF = 0.00165 (8/4834). AF 95% confidence interval is 0.000823. There are 0 homozygotes in GnomAd4. There are 42 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007327.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN1	NM_007327.4	MANE Select	c.693A>C	p.Val231Val	synonymous	Exon 5 of 20	NP_015566.1	Q05586-1
	GRIN1	NM_001437330.1		c.756A>C	p.Val252Val	synonymous	Exon 6 of 21	NP_001424259.1
	GRIN1	NM_001185090.2		c.756A>C	p.Val252Val	synonymous	Exon 6 of 21	NP_001172019.1	Q05586-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN1	ENST00000371561.8	TSL:1 MANE Select	c.693A>C	p.Val231Val	synonymous	Exon 5 of 20	ENSP00000360616.3	Q05586-1
	GRIN1	ENST00000371553.8	TSL:1	c.756A>C	p.Val252Val	synonymous	Exon 6 of 21	ENSP00000360608.3	Q05586-6
	GRIN1	ENST00000371560.5	TSL:1	c.756A>C	p.Val252Val	synonymous	Exon 6 of 20	ENSP00000360615.3	Q05586-7

Frequencies

GnomAD3 genomes AF: 0.000512 AC: 78 AN: 152210 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000542 AC: 120 AN: 221366 AF XY: 0.000574

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000216

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000546

Gnomad NFE exome AF: 0.000888

Gnomad OTH exome AF: 0.000360

GnomAD4 exome AF: 0.000825 AC: 1194 AN: 1446692 Hom.: 1 Cov.: 34 AF XY: 0.000860 AC XY: 618 AN XY: 718348

African (AFR) AF: 0.0000602 AC: 2 AN: 33200

American (AMR) AF: 0.000185 AC: 8 AN: 43208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25806

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38948

South Asian (SAS) AF: 0.00121 AC: 101 AN: 83814

European-Finnish (FIN) AF: 0.0000397 AC: 2 AN: 50434

Middle Eastern (MID) AF: 0.000903 AC: 5 AN: 5536

European-Non Finnish (NFE) AF: 0.000952 AC: 1053 AN: 1105940

Other (OTH) AF: 0.000368 AC: 22 AN: 59806

GnomAD4 genome AF: 0.000512 AC: 78 AN: 152328 Hom.: 0 Cov.: 34 AF XY: 0.000564 AC XY: 42 AN XY: 74492

African (AFR) AF: 0.000217 AC: 9 AN: 41566

American (AMR) AF: 0.00111 AC: 17 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00165 AC: 8 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000647 AC: 44 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000445 Hom.: 0

Bravo AF: 0.000484

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.57
PhyloP100		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs201818201; hg19: chr9-140051142;