Genetic Variant KCNJ10:c.1-84T>C (chr1-160042616-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002241.5(KCNJ10):c.1-84T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 1,177,116 control chromosomes in the GnomAD database, including 36,102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3413 hom., cov: 32)

Exomes 𝑓: 0.24 ( 32689 hom. )

Consequence

KCNJ10
NM_002241.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.295

Variant links:

Genes affected

KCNJ10 (HGNC:6256): (potassium inwardly rectifying channel subfamily J member 10) This gene encodes a member of the inward rectifier-type potassium channel family, characterized by having a greater tendency to allow potassium to flow into, rather than out of, a cell. The encoded protein may form a heterodimer with another potassium channel protein and may be responsible for the potassium buffering action of glial cells in the brain. Mutations in this gene have been associated with seizure susceptibility of common idiopathic generalized epilepsy syndromes. [provided by RefSeq, Jul 2008]

KCNJ10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 1-160042616-A-G is Benign according to our data. Variant chr1-160042616-A-G is described in ClinVar as [Benign]. Clinvar id is 1291083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ10	NM_002241.5 link	c.1-84T>C		intron_variant	Intron 1 of 1	ENST00000644903.1	NP_002232.2	P78508

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ10	ENST00000644903.1 link	c.1-84T>C		intron_variant	Intron 1 of 1		NM_002241.5	ENSP00000495557.1		P78508

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29323

AN:

152014

Hom.:

3416

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0723

Gnomad AMI

AF:

0.282

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.347

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.212

GnomAD4 exome

AF:

0.245

AC:

251015

AN:

1024984

Hom.:

32689

AF XY:

0.249

AC XY:

131672

AN XY:

527998

show subpopulations

Gnomad4 AFR exome

AF:

0.0667

Gnomad4 AMR exome

AF:

0.131

Gnomad4 ASJ exome

AF:

0.187

Gnomad4 EAS exome

AF:

0.246

Gnomad4 SAS exome

AF:

0.334

Gnomad4 FIN exome

AF:

0.206

Gnomad4 NFE exome

AF:

0.253

Gnomad4 OTH exome

AF:

0.237

GnomAD4 genome

AF:

0.193

AC:

29324

AN:

152132

Hom.:

3413

Cov.:

AF XY:

0.192

AC XY:

14290

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0725

Gnomad4 AMR

AF:

0.171

Gnomad4 ASJ

AF:

0.193

Gnomad4 EAS

AF:

0.242

Gnomad4 SAS

AF:

0.347

Gnomad4 FIN

AF:

0.192

Gnomad4 NFE

AF:

0.255

Gnomad4 OTH

AF:

0.210

Alfa

AF:

0.216

Hom.:

644

Bravo

AF:

0.181

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 25, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.18

DANN

Benign

0.51

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over