NM_139318.5:c.2020-1971A>G

Variant names:

• chr14-62710426-T-C
• rs869834
• NM_139318.5:c.2020-1971A>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.2020-1971A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,062 control chromosomes in the GnomAD database, including 10,906 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 0.37 (10906 hom., cov: 32)
• Consequence: KCNH5 NM_139318.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH5	NM_139318.5	c.2020-1971A>G		intron_variant	Intron 10 of 10	ENST00000322893.12	NP_647479.2
KCNH5	NM_172375.3	c.1823-1971A>G		intron_variant	Intron 9 of 9		NP_758963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH5	ENST00000322893.12	c.2020-1971A>G		intron_variant	Intron 10 of 10	1	NM_139318.5	ENSP00000321427.7
KCNH5	ENST00000420622.6	c.1823-1971A>G		intron_variant	Intron 9 of 9	1		ENSP00000395439.2

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56246 AN: 151944 Hom.: 10894 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.370 AC: 56282 AN: 152062 Hom.: 10906 Cov.: 32 AF XY: 0.371 AC XY: 27539 AN XY: 74318

African (AFR) AF: 0.299 AC: 12405 AN: 41496

American (AMR) AF: 0.414 AC: 6320 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1190 AN: 3468

East Asian (EAS) AF: 0.146 AC: 758 AN: 5180

South Asian (SAS) AF: 0.268 AC: 1292 AN: 4822

European-Finnish (FIN) AF: 0.443 AC: 4676 AN: 10546

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28438 AN: 67962

Other (OTH) AF: 0.366 AC: 773 AN: 2110

Alfa AF: 0.396 Hom.: 36528

Bravo AF: 0.363

Asia WGS AF: 0.219 AC: 762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.33
DANN	Benign	0.55
PhyloP100		-0.60
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: rs869834; hg19: chr14-63177144;