Genetic Variant KCNH5:c.198-10delT (chr14-63006481-GA-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_139318.5(KCNH5):c.198-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 1,465,854 control chromosomes in the GnomAD database, including 1,568 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.048 ( 203 hom., cov: 32)

Exomes 𝑓: 0.043 ( 1365 hom. )

Consequence

KCNH5
NM_139318.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.114

Publications

2 publications found

Variant links:

Genes affected

KCNH5 (HGNC:6254): (potassium voltage-gated channel subfamily H member 5) This gene encodes a member of voltage-gated potassium channels. Members of this family have diverse functions, including regulating neurotransmitter and hormone release, cardiac function, and cell volume. This protein is an outward-rectifying, noninactivating channel. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

KCNH5 Gene-Disease associations (from GenCC):

infantile-onset epilepsy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
developmental and epileptic encephalopathy 112
Inheritance: AD Classification: STRONG Submitted by: G2P

KCNH5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 14-63006481-GA-G is Benign according to our data. Variant chr14-63006481-GA-G is described in ClinVar as Benign. ClinVar VariationId is 241862.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0571 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139318.5. 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
	KCNH5	NM_139318.5	MANE Select	c.198-10delT		intron	N/A	NP_647479.2
	KCNH5	NM_172375.3		c.198-10delT		intron	N/A	NP_758963.1	Q8NCM2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNH5	ENST00000322893.12	TSL:1 MANE Select	c.198-10delT	intron	N/A	ENSP00000321427.7	Q8NCM2-1
KCNH5	ENST00000420622.6	TSL:1	c.198-10delT	intron	N/A	ENSP00000395439.2	Q8NCM2-2
KCNH5	ENST00000394964.3	TSL:1	n.363-10delT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0479

AC:

7256

AN:

151510

Hom.:

202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0485

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.0356

Gnomad ASJ

AF:

0.0188

Gnomad EAS

AF:

0.0630

Gnomad SAS

AF:

0.0217

Gnomad FIN

AF:

0.0917

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0454

Gnomad OTH

AF:

0.0376

GnomAD2 exomes

AF:

0.0468

AC:

10735

AN:

229392

AF XY:

0.0450

show subpopulations

Gnomad AFR exome

AF:

0.0506

Gnomad AMR exome

AF:

0.0309

Gnomad ASJ exome

AF:

0.0244

Gnomad EAS exome

AF:

0.0700

Gnomad FIN exome

AF:

0.0887

Gnomad NFE exome

AF:

0.0484

Gnomad OTH exome

AF:

0.0430

GnomAD4 exome

AF:

0.0427

AC:

56092

AN:

1314228

Hom.:

1365

Cov.:

AF XY:

0.0421

AC XY:

27752

AN XY:

659622

show subpopulations

African (AFR)

AF:

0.0495

AC:

1485

AN:

30030

American (AMR)

AF:

0.0298

AC:

1242

AN:

41688

Ashkenazi Jewish (ASJ)

AF:

0.0212

AC:

524

AN:

24726

East Asian (EAS)

AF:

0.0528

AC:

2043

AN:

38684

South Asian (SAS)

AF:

0.0170

AC:

1357

AN:

79972

European-Finnish (FIN)

AF:

0.0830

AC:

4300

AN:

51804

Middle Eastern (MID)

AF:

0.0190

AC:

103

AN:

5424

European-Non Finnish (NFE)

AF:

0.0435

AC:

42886

AN:

986736

Other (OTH)

AF:

0.0390

AC:

2152

AN:

55164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

2521

5041

7562

10082

12603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1522

3044

4566

6088

7610

<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:

0.0479

AC:

7258

AN:

151626

Hom.:

203

Cov.:

AF XY:

0.0494

AC XY:

3658

AN XY:

74040

show subpopulations

African (AFR)

AF:

0.0485

AC:

2006

AN:

41376

American (AMR)

AF:

0.0356

AC:

542

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.0188

AC:

AN:

3458

East Asian (EAS)

AF:

0.0627

AC:

324

AN:

5166

South Asian (SAS)

AF:

0.0217

AC:

104

AN:

4784

European-Finnish (FIN)

AF:

0.0917

AC:

958

AN:

10442

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0454

AC:

3082

AN:

67870

Other (OTH)

AF:

0.0367

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

340

681

1021

1362

1702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0232

Hom.:

Bravo

AF:

0.0445

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Developmental and epileptic encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.11

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.

14-63006481-GAA-GA

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