chr14-62834639-T-C

Variant names:

• chr14-62834639-T-C
• rs243149
• NM_139318.5:c.1569+15014A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139318.5(KCNH5):​c.1569+15014A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,762 control chromosomes in the GnomAD database, including 9,056 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (9056 hom., cov: 31)
• Consequence: KCNH5 NM_139318.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.567 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH5	NM_139318.5	MANE Select	c.1569+15014A>G		intron	N/A	NP_647479.2
	KCNH5	NM_172375.3		c.1569+15014A>G		intron	N/A	NP_758963.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH5	ENST00000322893.12	TSL:1 MANE Select	c.1569+15014A>G		intron	N/A	ENSP00000321427.7
	KCNH5	ENST00000420622.6	TSL:1	c.1569+15014A>G		intron	N/A	ENSP00000395439.2
	KCNH5	ENST00000394968.2	TSL:2	c.1395+15014A>G		intron	N/A	ENSP00000378419.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49888 AN: 151644 Hom.: 9064 Cov.: 31

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.346

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.329 AC: 49878 AN: 151762 Hom.: 9056 Cov.: 31 AF XY: 0.336 AC XY: 24949 AN XY: 74160

African (AFR) AF: 0.189 AC: 7821 AN: 41472

American (AMR) AF: 0.279 AC: 4252 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1461 AN: 3462

East Asian (EAS) AF: 0.481 AC: 2489 AN: 5170

South Asian (SAS) AF: 0.585 AC: 2820 AN: 4820

European-Finnish (FIN) AF: 0.455 AC: 4799 AN: 10544

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.368 AC: 24951 AN: 67744

Other (OTH) AF: 0.347 AC: 731 AN: 2108

Alfa AF: 0.358 Hom.: 16834

Bravo AF: 0.304

Asia WGS AF: 0.471 AC: 1636 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.4
DANN	Benign	0.72
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs243149; hg19: chr14-63301357;