Genetic Variant NM_002241.5:c.1-84T>C (chr1-160042616-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

EAST syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
Pendred syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
enlarged vestibular aqueduct syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

KCNJ10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002241.5. 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
	KCNJ10	NM_002241.5	MANE Select	c.1-84T>C		intron	N/A	NP_002232.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNJ10	ENST00000644903.1	MANE Select	c.1-84T>C	intron	N/A	ENSP00000495557.1	P78508
KCNJ10	ENST00000638728.1	TSL:5	c.1-84T>C	intron	N/A	ENSP00000492619.1	P78508
KCNJ10	ENST00000638868.1	TSL:5	c.1-84T>C	intron	N/A	ENSP00000491250.1	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

African (AFR)

AF:

0.0667

AC:

1687

AN:

25308

American (AMR)

AF:

0.131

AC:

5509

AN:

42046

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

4375

AN:

23360

East Asian (EAS)

AF:

0.246

AC:

9171

AN:

37344

South Asian (SAS)

AF:

0.334

AC:

25331

AN:

75940

European-Finnish (FIN)

AF:

0.206

AC:

8865

AN:

43058

Middle Eastern (MID)

AF:

0.232

AC:

1155

AN:

4972

European-Non Finnish (NFE)

AF:

0.253

AC:

183975

AN:

726816

Other (OTH)

AF:

0.237

AC:

10947

AN:

46140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

10178

20357

30535

40714

50892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4942

9884

14826

19768

24710

<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:

0.193

AC:

29324

AN:

152132

Hom.:

3413

Cov.:

AF XY:

0.192

AC XY:

14290

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0725

AC:

3010

AN:

41530

American (AMR)

AF:

0.171

AC:

2612

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

670

AN:

3468

East Asian (EAS)

AF:

0.242

AC:

1249

AN:

5164

South Asian (SAS)

AF:

0.347

AC:

1669

AN:

4812

European-Finnish (FIN)

AF:

0.192

AC:

2032

AN:

10568

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.255

AC:

17327

AN:

67986

Other (OTH)

AF:

0.210

AC:

444

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1137

2273

3410

4546

5683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

330

660

990

1320

1650

<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:

0.216

Hom.:

644

Bravo

AF:

0.181

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.18

(source)

DANN

Benign

0.51

PhyloP100

-0.29

PromoterAI

-0.0058

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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