NM_139318.5:c.2020-17775A>G

Variant names:

• chr14-62726230-T-C
• rs2101552
• NM_139318.5:c.2020-17775A>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.2020-17775A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.931 in 152,226 control chromosomes in the GnomAD database, including 66,634 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 0.93 (66634 hom., cov: 31)
• Consequence: KCNH5 NM_139318.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.99 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.2020-17775A>G		intron	N/A	NP_647479.2
	KCNH5	NM_172375.3		c.1823-17775A>G		intron	N/A	NP_758963.1	Q8NCM2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH5	ENST00000322893.12	TSL:1 MANE Select	c.2020-17775A>G		intron	N/A	ENSP00000321427.7	Q8NCM2-1
	KCNH5	ENST00000420622.6	TSL:1	c.1823-17775A>G		intron	N/A	ENSP00000395439.2	Q8NCM2-2
	KCNH5	ENST00000394968.2	TSL:2	c.1846-13514A>G		intron	N/A	ENSP00000378419.1	Q8NCM2-3

Frequencies

GnomAD3 genomes AF: 0.931 AC: 141624 AN: 152108 Hom.: 66582 Cov.: 31

Gnomad AFR AF: 0.788

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.964

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.987

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.937

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

GnomAD4 genome AF: 0.931 AC: 141734 AN: 152226 Hom.: 66634 Cov.: 31 AF XY: 0.932 AC XY: 69347 AN XY: 74420

African (AFR) AF: 0.788 AC: 32709 AN: 41510

American (AMR) AF: 0.964 AC: 14748 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.977 AC: 3391 AN: 3472

East Asian (EAS) AF: 0.907 AC: 4696 AN: 5178

South Asian (SAS) AF: 0.988 AC: 4762 AN: 4822

European-Finnish (FIN) AF: 0.987 AC: 10465 AN: 10606

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.997 AC: 67789 AN: 68018

Other (OTH) AF: 0.937 AC: 1982 AN: 2116

Alfa AF: 0.953 Hom.: 8992

Bravo AF: 0.923

Asia WGS AF: 0.946 AC: 3279 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.074
DANN	Benign	0.20
PhyloP100		-1.4
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: rs2101552; hg19: chr14-63192948;