dbSNP rs782424418: GRIK5:p.Ala902Ala (chr19-41999108-C-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_002088.5(GRIK5):c.2706G>T(p.Ala902Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000219 in 1,370,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

GRIK5
NM_002088.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.280

Publications

0 publications found

Variant links:

Genes affected

GRIK5 (HGNC:4583): (glutamate ionotropic receptor kainate type subunit 5) 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

GRIK5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 19-41999108-C-A is Benign according to our data. Variant chr19-41999108-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2649936.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.28 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002088.5. 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
	GRIK5	NM_002088.5	MANE Select	c.2706G>T	p.Ala902Ala	synonymous	Exon 20 of 20	NP_002079.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GRIK5	ENST00000593562.6	TSL:5 MANE Select	c.2706G>T	p.Ala902Ala	synonymous	Exon 20 of 20	ENSP00000470251.1	Q16478-1
GRIK5	ENST00000262895.7	TSL:1	c.2706G>T	p.Ala902Ala	synonymous	Exon 19 of 19	ENSP00000262895.2	Q16478-1
GRIK5	ENST00000454993.6	TSL:1	n.1583G>T		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes

AF:

0.00000664

AC:

AN:

150614

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000164

AC:

AN:

1219546

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

596966

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23872

American (AMR)

AF:

0.00

AC:

AN:

13616

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18062

East Asian (EAS)

AF:

0.00

AC:

AN:

26434

South Asian (SAS)

AF:

0.00

AC:

AN:

54774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29638

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3454

European-Non Finnish (NFE)

AF:

0.00000200

AC:

AN:

999946

Other (OTH)

AF:

0.00

AC:

AN:

49750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000664

AC:

AN:

150614

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73480

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41276

American (AMR)

AF:

0.00

AC:

AN:

15160

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3426

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10254

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67216

Other (OTH)

AF:

0.00

AC:

AN:

2068

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

-0.28

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over