Variant chr14-63006481-GA-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_139318.5(KCNH5):c.198-10del variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.114

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
KCNH5	NM_139318.5 linkuse as main transcript	c.198-10del	splice_polypyrimidine_tract_variant, intron_variant	ENST00000322893.12	NP_647479.2
KCNH5	NM_172375.3 linkuse as main transcript	c.198-10del	splice_polypyrimidine_tract_variant, intron_variant		NP_758963.1
KCNH5	XM_047431275.1 linkuse as main transcript	c.198-10del	splice_polypyrimidine_tract_variant, intron_variant		XP_047287231.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
KCNH5	ENST00000322893.12 linkuse as main transcript	c.198-10del	splice_polypyrimidine_tract_variant, intron_variant	1	NM_139318.5	ENSP00000321427	P1	Q8NCM2-1
KCNH5	ENST00000420622.6 linkuse as main transcript	c.198-10del	splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000395439		Q8NCM2-2
KCNH5	ENST00000394964.3 linkuse as main transcript	n.363-10del	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	1
KCNH5	ENST00000394968.2 linkuse as main transcript	c.24-10del	splice_polypyrimidine_tract_variant, intron_variant	2		ENSP00000378419		Q8NCM2-3

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

GnomAD3 exomes

AF:

0.0468

AC:

10735

AN:

229392

Hom.:

293

AF XY:

0.0450

AC XY:

5594

AN XY:

124210

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 SAS exome

AF:

0.0187

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

Gnomad4 AFR exome

AF:

0.0495

Gnomad4 AMR exome

AF:

0.0298

Gnomad4 ASJ exome

AF:

0.0212

Gnomad4 EAS exome

AF:

0.0528

Gnomad4 SAS exome

AF:

0.0170

Gnomad4 FIN exome

AF:

0.0830

Gnomad4 NFE exome

AF:

0.0435

Gnomad4 OTH exome

AF:

0.0390

GnomAD4 genome

AF:

0.0479

AC:

7258

AN:

151626

Hom.:

203

Cov.:

AF XY:

0.0494

AC XY:

3658

AN XY:

74040

show subpopulations

Gnomad4 AFR

AF:

0.0485

Gnomad4 AMR

AF:

0.0356

Gnomad4 ASJ

AF:

0.0188

Gnomad4 EAS

AF:

0.0627

Gnomad4 SAS

AF:

0.0217

Gnomad4 FIN

AF:

0.0917

Gnomad4 NFE

AF:

0.0454

Gnomad4 OTH

AF:

0.0367

Alfa

AF:

0.0232

Hom.:

Bravo

AF:

0.0445

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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