Menu
GeneBe

22-38427131-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_152868.3(KCNJ4):c.1002A>G(p.Ser334=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 1,612,554 control chromosomes in the GnomAD database, including 350,395 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.70 ( 38630 hom., cov: 30)
Exomes 𝑓: 0.65 ( 311765 hom. )

Consequence

KCNJ4
NM_152868.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.66
Variant links:
Genes affected
KCNJ4 (HGNC:6265): (potassium inwardly rectifying channel subfamily J member 4) Several different potassium channels are known to be involved with electrical signaling in the nervous system. One class is activated by depolarization whereas a second class is not. The latter are referred to as inwardly rectifying K+ channels, and they have a greater tendency to allow potassium to flow into the cell rather than out of it. This asymmetry in potassium ion conductance plays a key role in the excitability of muscle cells and neurons. The protein encoded by this gene is an integral membrane protein and member of the inward rectifier potassium channel family. The encoded protein has a small unitary conductance compared to other members of this protein family. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-38427131-T-C is Benign according to our data. Variant chr22-38427131-T-C is described in ClinVar as [Benign]. Clinvar id is 1274320.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-5.66 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KCNJ4NM_152868.3 linkuse as main transcriptc.1002A>G p.Ser334= synonymous_variant 2/2 ENST00000303592.3
LOC101927183XR_938252.3 linkuse as main transcriptn.306+2159T>C intron_variant, non_coding_transcript_variant
KCNJ4NM_004981.2 linkuse as main transcriptc.1002A>G p.Ser334= synonymous_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KCNJ4ENST00000303592.3 linkuse as main transcriptc.1002A>G p.Ser334= synonymous_variant 2/21 NM_152868.3 P1
ENST00000433230.1 linkuse as main transcriptn.351T>C non_coding_transcript_exon_variant 3/32

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.704
AC:
106867
AN:
151848
Hom.:
38574
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.840
Gnomad AMI
AF:
0.588
Gnomad AMR
AF:
0.668
Gnomad ASJ
AF:
0.617
Gnomad EAS
AF:
0.933
Gnomad SAS
AF:
0.868
Gnomad FIN
AF:
0.671
Gnomad MID
AF:
0.630
Gnomad NFE
AF:
0.612
Gnomad OTH
AF:
0.696
GnomAD3 exomes
AF:
0.697
AC:
173615
AN:
249012
Hom.:
62264
AF XY:
0.700
AC XY:
94617
AN XY:
135120
show subpopulations
Gnomad AFR exome
AF:
0.847
Gnomad AMR exome
AF:
0.678
Gnomad ASJ exome
AF:
0.604
Gnomad EAS exome
AF:
0.939
Gnomad SAS exome
AF:
0.865
Gnomad FIN exome
AF:
0.667
Gnomad NFE exome
AF:
0.612
Gnomad OTH exome
AF:
0.668
GnomAD4 exome
AF:
0.647
AC:
945651
AN:
1460588
Hom.:
311765
Cov.:
65
AF XY:
0.653
AC XY:
474581
AN XY:
726596
show subpopulations
Gnomad4 AFR exome
AF:
0.847
Gnomad4 AMR exome
AF:
0.677
Gnomad4 ASJ exome
AF:
0.606
Gnomad4 EAS exome
AF:
0.947
Gnomad4 SAS exome
AF:
0.859
Gnomad4 FIN exome
AF:
0.657
Gnomad4 NFE exome
AF:
0.612
Gnomad4 OTH exome
AF:
0.671
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.704
AC:
106979
AN:
151966
Hom.:
38630
Cov.:
30
AF XY:
0.710
AC XY:
52722
AN XY:
74266
show subpopulations
Gnomad4 AFR
AF:
0.840
Gnomad4 AMR
AF:
0.668
Gnomad4 ASJ
AF:
0.617
Gnomad4 EAS
AF:
0.933
Gnomad4 SAS
AF:
0.869
Gnomad4 FIN
AF:
0.671
Gnomad4 NFE
AF:
0.612
Gnomad4 OTH
AF:
0.700
Alfa
AF:
0.637
Hom.:
42732
Bravo
AF:
0.707
Asia WGS
AF:
0.899
AC:
3126
AN:
3478
EpiCase
AF:
0.624
EpiControl
AF:
0.618

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxApr 16, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
Cadd
Benign
0.13
Dann
Benign
0.47

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs196059; hg19: chr22-38823136; COSMIC: COSV57858134; API