Genetic Variant GRIK3:c.733-149C>T (chr1-36869950-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000831.4(GRIK3):c.733-149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 650,926 control chromosomes in the GnomAD database, including 268,510 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 0.86 ( 56992 hom., cov: 33)

Exomes 𝑓: 0.92 ( 211518 hom. )

Consequence

GRIK3
NM_000831.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0940

Publications

4 publications found

Variant links:

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]

GRIK3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK3	NM_000831.4 link	c.733-149C>T		intron_variant	Intron 4 of 15	ENST00000373091.8	NP_000822.2	Q13003-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK3	ENST00000373091.8 link	c.733-149C>T		intron_variant	Intron 4 of 15	1	NM_000831.4	ENSP00000362183.3		Q13003-1
GRIK3	ENST00000373093.4 link	c.733-149C>T		intron_variant	Intron 4 of 14	1		ENSP00000362185.4		Q13003-2

Frequencies

GnomAD3 genomes

AF:

0.858

AC:

130553

AN:

152138

Hom.:

56979

Cov.:

show subpopulations

Gnomad AFR

AF:

0.679

Gnomad AMI

AF:

0.898

Gnomad AMR

AF:

0.929

Gnomad ASJ

AF:

0.857

Gnomad EAS

AF:

0.950

Gnomad SAS

AF:

0.934

Gnomad FIN

AF:

0.932

Gnomad MID

AF:

0.858

Gnomad NFE

AF:

0.926

Gnomad OTH

AF:

0.876

GnomAD4 exome

AF:

0.920

AC:

458573

AN:

498670

Hom.:

211518

AF XY:

0.921

AC XY:

245153

AN XY:

266282

show subpopulations

African (AFR)

AF:

0.684

AC:

9973

AN:

14584

American (AMR)

AF:

0.943

AC:

27480

AN:

29136

Ashkenazi Jewish (ASJ)

AF:

0.845

AC:

13435

AN:

15908

East Asian (EAS)

AF:

0.971

AC:

30749

AN:

31654

South Asian (SAS)

AF:

0.926

AC:

48530

AN:

52396

European-Finnish (FIN)

AF:

0.936

AC:

31543

AN:

33696

Middle Eastern (MID)

AF:

0.880

AC:

2028

AN:

2304

European-Non Finnish (NFE)

AF:

0.927

AC:

269583

AN:

290844

Other (OTH)

AF:

0.897

AC:

25252

AN:

28148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1780

3559

5339

7118

8898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1012

2024

3036

4048

5060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.858

AC:

130609

AN:

152256

Hom.:

56992

Cov.:

AF XY:

0.861

AC XY:

64077

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.678

AC:

28153

AN:

41506

American (AMR)

AF:

0.929

AC:

14222

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.857

AC:

2975

AN:

3472

East Asian (EAS)

AF:

0.950

AC:

4911

AN:

5172

South Asian (SAS)

AF:

0.935

AC:

4514

AN:

4830

European-Finnish (FIN)

AF:

0.932

AC:

9895

AN:

10614

Middle Eastern (MID)

AF:

0.854

AC:

251

AN:

294

European-Non Finnish (NFE)

AF:

0.926

AC:

63014

AN:

68032

Other (OTH)

AF:

0.877

AC:

1855

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

865

1730

2596

3461

4326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

886

1772

2658

3544

4430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.862

Hom.:

43489

Bravo

AF:

0.848

Asia WGS

AF:

0.902

AC:

3134

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

9.8

(source)

DANN

Benign

0.59

PhyloP100

0.094

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over