rs243146

Variant names:

• chr14-62838427-A-G
• rs243146
• NM_139318.5:c.1569+11226T>C

Your query was ambiguous. Multiple possible variants found:

• chr14-62838427-A-G
• chr14-62838427-A-T

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+11226T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,012 control chromosomes in the GnomAD database, including 8,538 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 0.31 (8538 hom., cov: 32)
• Consequence: KCNH5 NM_139318.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• Publications: 1 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH5	NM_139318.5	c.1569+11226T>C		intron_variant	Intron 8 of 10	ENST00000322893.12	NP_647479.2
KCNH5	NM_172375.3	c.1569+11226T>C		intron_variant	Intron 8 of 9		NP_758963.1
KCNH5	XM_047431275.1	c.1569+11226T>C		intron_variant	Intron 8 of 9		XP_047287231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH5	ENST00000322893.12	c.1569+11226T>C		intron_variant	Intron 8 of 10	1	NM_139318.5	ENSP00000321427.7
KCNH5	ENST00000420622.6	c.1569+11226T>C		intron_variant	Intron 8 of 9	1		ENSP00000395439.2
KCNH5	ENST00000394968.2	c.1395+11226T>C		intron_variant	Intron 8 of 10	2		ENSP00000378419.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47328 AN: 151894 Hom.: 8547 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.311 AC: 47314 AN: 152012 Hom.: 8538 Cov.: 32 AF XY: 0.319 AC XY: 23733 AN XY: 74302

African (AFR) AF: 0.135 AC: 5588 AN: 41504

American (AMR) AF: 0.273 AC: 4159 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1431 AN: 3472

East Asian (EAS) AF: 0.466 AC: 2406 AN: 5168

South Asian (SAS) AF: 0.582 AC: 2807 AN: 4822

European-Finnish (FIN) AF: 0.453 AC: 4780 AN: 10544

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24892 AN: 67934

Other (OTH) AF: 0.330 AC: 698 AN: 2112

Alfa AF: 0.309 Hom.: 1237

Bravo AF: 0.284

Asia WGS AF: 0.462 AC: 1606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.81
PhyloP100		-0.27
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: rs243146; hg19: chr14-63305145;