dbSNP rs5016722: GRIK4:c.*33C>A (chr11-120986293-C-A) – 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>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00061 in 241,130 control chromosomes in the GnomAD database, including 1 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 0.000021 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00099 ( 1 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:

Genome browser will be placed here

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=-0.69).

BS2

High AC in GnomAdExome4 at 145 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
GRIK4	NM_014619.5	MANE Select	c.*33C>A	3_prime_UTR	Exon 21 of 21	NP_055434.2
GRIK4	NM_001282470.3		c.*33C>A	3_prime_UTR	Exon 20 of 20	NP_001269399.1
GRIK4	NM_001440402.1		c.*33C>A	3_prime_UTR	Exon 23 of 23	NP_001427331.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.0000210

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:

0.000190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000252

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00245

AC:

178

AN:

72766

AF XY:

0.00240

show subpopulations

Gnomad AFR exome

AF:

0.00321

Gnomad AMR exome

AF:

0.00174

Gnomad ASJ exome

AF:

0.00196

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00379

Gnomad NFE exome

AF:

0.00335

Gnomad OTH exome

AF:

0.00209

GnomAD4 exome

AF:

0.000994

AC:

145

AN:

145822

Hom.:

Cov.:

AF XY:

0.000979

AC XY:

AN XY:

82772

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

2624

American (AMR)

AF:

0.000922

AC:

AN:

8676

Ashkenazi Jewish (ASJ)

AF:

0.000911

AC:

AN:

3294

East Asian (EAS)

AF:

0.000210

AC:

AN:

4762

South Asian (SAS)

AF:

0.000312

AC:

AN:

28848

European-Finnish (FIN)

AF:

0.000876

AC:

AN:

5710

Middle Eastern (MID)

AF:

0.00242

AC:

AN:

414

European-Non Finnish (NFE)

AF:

0.00133

AC:

113

AN:

85228

Other (OTH)

AF:

0.000319

AC:

AN:

6266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

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:

0.0000210

AC:

AN:

95308

Hom.:

Cov.:

AF XY:

0.0000430

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:

0.000190

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: 0.475

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

Alfa

AF:

0.00464

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.55

(source)

DANN

Benign

0.90

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