Variant chr14-62708387-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_139318.5(KCNH5):c.2088G>A(p.Val696Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 1,613,142 control chromosomes in the GnomAD database, including 1,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 118 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1241 hom. )

Consequence

KCNH5
NM_139318.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.192

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 14-62708387-C-T is Benign according to our data. Variant chr14-62708387-C-T is described in ClinVar as [Benign]. Clinvar id is 416125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.192 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH5	NM_139318.5 linkuse as main transcript	c.2088G>A	p.Val696Val	synonymous_variant	11/11	ENST00000322893.12	NP_647479.2	Q8NCM2-1
KCNH5	NM_172375.3 linkuse as main transcript	c.*55G>A		3_prime_UTR_variant	10/10		NP_758963.1	Q8NCM2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNH5	ENST00000322893.12 linkuse as main transcript	c.2088G>A	p.Val696Val	synonymous_variant	11/11	1	NM_139318.5	ENSP00000321427.7		Q8NCM2-1
KCNH5	ENST00000420622 linkuse as main transcript	c.*55G>A		3_prime_UTR_variant	10/10	1		ENSP00000395439.2		Q8NCM2-2

Frequencies

GnomAD3 genomes

AF:

0.0306

AC:

4650

AN:

152100

Hom.:

118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00618

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0204

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.0679

Gnomad FIN

AF:

0.0733

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0415

Gnomad OTH

AF:

0.0292

GnomAD3 exomes

AF:

0.0347

AC:

8697

AN:

250560

Hom.:

249

AF XY:

0.0361

AC XY:

4885

AN XY:

135488

show subpopulations

Gnomad AFR exome

AF:

0.00517

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.00586

Gnomad EAS exome

AF:

0.00120

Gnomad SAS exome

AF:

0.0630

Gnomad FIN exome

AF:

0.0747

Gnomad NFE exome

AF:

0.0396

Gnomad OTH exome

AF:

0.0295

GnomAD4 exome

AF:

0.0371

AC:

54211

AN:

1460924

Hom.:

1241

Cov.:

AF XY:

0.0378

AC XY:

27460

AN XY:

726772

show subpopulations

Gnomad4 AFR exome

AF:

0.00448

Gnomad4 AMR exome

AF:

0.0122

Gnomad4 ASJ exome

AF:

0.00643

Gnomad4 EAS exome

AF:

0.00340

Gnomad4 SAS exome

AF:

0.0609

Gnomad4 FIN exome

AF:

0.0716

Gnomad4 NFE exome

AF:

0.0380

Gnomad4 OTH exome

AF:

0.0310

GnomAD4 genome

AF:

0.0306

AC:

4655

AN:

152218

Hom.:

118

Cov.:

AF XY:

0.0325

AC XY:

2416

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00616

Gnomad4 AMR

AF:

0.0203

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0680

Gnomad4 FIN

AF:

0.0733

Gnomad4 NFE

AF:

0.0415

Gnomad4 OTH

AF:

0.0313

Alfa

AF:

0.0351

Hom.:

204

Bravo

AF:

0.0237

Asia WGS

AF:

0.0600

AC:

209

AN:

3478

EpiCase

AF:

0.0327

EpiControl

AF:

0.0328

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

KCNH5-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.2

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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