14-62799180-G-T

Variant names:

• chr14-62799180-G-T
• rs2065632
• NM_139318.5:c.1822+3149C>A

Variant summary

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

The NM_139318.5(KCNH5):​c.1822+3149C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 151,948 control chromosomes in the GnomAD database, including 26,410 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 0.59 (26410 hom., cov: 32)
• Consequence: KCNH5 NM_139318.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH5	NM_139318.5	c.1822+3149C>A		intron_variant	Intron 9 of 10	ENST00000322893.12	NP_647479.2
KCNH5	NM_172375.3	c.1822+3149C>A		intron_variant	Intron 9 of 9		NP_758963.1
KCNH5	XM_047431275.1	c.1806+3165C>A		intron_variant	Intron 9 of 9		XP_047287231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH5	ENST00000322893.12	c.1822+3149C>A		intron_variant	Intron 9 of 10	1	NM_139318.5	ENSP00000321427.7
KCNH5	ENST00000420622.6	c.1822+3149C>A		intron_variant	Intron 9 of 9	1		ENSP00000395439.2
KCNH5	ENST00000394968.2	c.1648+3149C>A		intron_variant	Intron 9 of 10	2		ENSP00000378419.1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88860 AN: 151830 Hom.: 26362 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.585 AC: 88961 AN: 151948 Hom.: 26410 Cov.: 32 AF XY: 0.588 AC XY: 43627 AN XY: 74226

African (AFR) AF: 0.540 AC: 22357 AN: 41412

American (AMR) AF: 0.585 AC: 8925 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2307 AN: 3470

East Asian (EAS) AF: 0.768 AC: 3963 AN: 5160

South Asian (SAS) AF: 0.821 AC: 3953 AN: 4816

European-Finnish (FIN) AF: 0.536 AC: 5652 AN: 10536

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39846 AN: 67978

Other (OTH) AF: 0.595 AC: 1256 AN: 2110

Alfa AF: 0.588 Hom.: 49116

Bravo AF: 0.588

Asia WGS AF: 0.777 AC: 2702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.29
DANN	Benign	0.68
PhyloP100		-0.67
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: rs2065632; hg19: chr14-63265898;