Genetic Variant GRIK4:c.*33C>T (chr11-120986293-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014619.5(GRIK4):c.*33C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000456 in 241,152 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000010 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

GRIK4
NM_014619.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.26

Publications

2 publications found

Variant links:

Genes affected

GRIK4 (HGNC:4582): (glutamate ionotropic receptor kainate type subunit 4) This gene encodes a protein that belongs to the glutamate-gated ionic channel family. Glutamate functions as the major excitatory neurotransmitter in the central nervous system through activation of ligand-gated ion channels and G protein-coupled membrane receptors. The protein encoded by this gene forms functional heteromeric kainate-preferring ionic channels with the subunits encoded by related gene family members. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

GRIK4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014619.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GRIK4	NM_014619.5	MANE Select	c.*33C>T	3_prime_UTR	Exon 21 of 21	NP_055434.2
GRIK4	NM_001282470.3		c.*33C>T	3_prime_UTR	Exon 20 of 20	NP_001269399.1	A0A8D9PH79
GRIK4	NM_001440402.1		c.*33C>T	3_prime_UTR	Exon 23 of 23	NP_001427331.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GRIK4	ENST00000527524.8	TSL:2 MANE Select	c.*33C>T	3_prime_UTR	Exon 21 of 21	ENSP00000435648.2	Q16099
GRIK4	ENST00000438375.2	TSL:1	c.*33C>T	3_prime_UTR	Exon 20 of 20	ENSP00000404063.2	Q16099
GRIK4	ENST00000638419.1	TSL:5	c.*33C>T	3_prime_UTR	Exon 21 of 21	ENSP00000492086.1	Q16099

Frequencies

GnomAD3 genomes

AF:

0.0000105

AC:

AN:

95308

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000252

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000412

AC:

AN:

72766

AF XY:

0.0000233

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000866

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000686

AC:

AN:

145844

Hom.:

Cov.:

AF XY:

0.0000483

AC XY:

AN XY:

82786

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

2624

American (AMR)

AF:

0.00

AC:

AN:

8678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3296

East Asian (EAS)

AF:

0.00

AC:

AN:

4762

South Asian (SAS)

AF:

0.00

AC:

AN:

28850

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5712

Middle Eastern (MID)

AF:

0.00

AC:

AN:

414

European-Non Finnish (NFE)

AF:

0.000117

AC:

AN:

85240

Other (OTH)

AF:

0.00

AC:

AN:

6268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000105

AC:

AN:

95308

Hom.:

Cov.:

AF XY:

0.0000215

AC XY:

AN XY:

46540

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29402

American (AMR)

AF:

0.00

AC:

AN:

10344

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1928

East Asian (EAS)

AF:

0.00

AC:

AN:

3838

South Asian (SAS)

AF:

0.00

AC:

AN:

3038

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

152

European-Non Finnish (NFE)

AF:

0.0000252

AC:

AN:

39682

Other (OTH)

AF:

0.00

AC:

AN:

1288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

1.2

(source)

DANN

Benign

0.95

PhyloP100

-3.3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over