rs499610

Variant names:

• chr1-37003045-G-A
• rs499610
• NM_000831.4:c.115+30949C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000831.4(GRIK3):​c.115+30949C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0000076 (0 hom., cov: 29)
  • Failed GnomAD Quality Control
• Consequence: GRIK3 NM_000831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.971
• Publications: 1 publications found

Genes affected

GRIK3 (HGNC:4581): (glutamate ionotropic receptor kainate type subunit 3) Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to the kainate family of glutamate receptors, which are composed of four subunits and function as ligand-activated ion channels. It is not certain if the subunit encoded by this gene is subject to RNA editing as the other 2 family members (GRIK1 and GRIK2). A Ser310Ala polymorphism has been associated with schizophrenia, and there are conflicting reports of its association with the pathogenesis of delirium tremens in alcoholics. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK3	NM_000831.4	c.115+30949C>T		intron_variant	Intron 1 of 15	ENST00000373091.8	NP_000822.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK3	ENST00000373091.8	c.115+30949C>T		intron_variant	Intron 1 of 15	1	NM_000831.4	ENSP00000362183.3
GRIK3	ENST00000373093.4	c.115+30949C>T		intron_variant	Intron 1 of 14	1		ENSP00000362185.4

Frequencies

GnomAD3 genomes AF: 0.00000764 AC: 1 AN: 130934 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000142

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000764 AC: 1 AN: 130934 Hom.: 0 Cov.: 29 AF XY: 0.0000160 AC XY: 1 AN XY: 62438

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32408

American (AMR) AF: 0.00 AC: 0 AN: 12622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3322

East Asian (EAS) AF: 0.00 AC: 0 AN: 4560

South Asian (SAS) AF: 0.00 AC: 0 AN: 4172

European-Finnish (FIN) AF: 0.000142 AC: 1 AN: 7044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 248

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 63896

Other (OTH) AF: 0.00 AC: 0 AN: 1816

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.9
DANN	Benign	0.64
PhyloP100		0.97

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

Other links and lift over

dbSNP: rs499610; hg19: chr1-37468646;