rs243144

chr14-62803403-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139318.5(KCNH5):c.1570-822G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 152,192 control chromosomes in the GnomAD database, including 148 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 0.038 (148 hom., cov: 32)
• Consequence: KCNH5 NM_139318.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNH5	NM_139318.5	c.1570-822G>T		intron_variant		ENST00000322893.12
KCNH5	NM_172375.3	c.1570-822G>T		intron_variant
KCNH5	XM_047431275.1	c.1570-822G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNH5	ENST00000322893.12	c.1570-822G>T		intron_variant		1	NM_139318.5	P1
KCNH5	ENST00000420622.6	c.1570-822G>T		intron_variant		1
KCNH5	ENST00000394968.2	c.1396-822G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0383 AC: 5817 AN: 152074 Hom.: 148 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0363

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00787

Gnomad FIN AF: 0.0735

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0562

Gnomad OTH AF: 0.0379

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

GnomAD4 genome AF: 0.0382 AC: 5814 AN: 152192 Hom.: 148 Cov.: 32 AF XY: 0.0384 AC XY: 2855 AN XY: 74384

Gnomad4 AFR AF: 0.0103

Gnomad4 AMR AF: 0.0363

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00787

Gnomad4 FIN AF: 0.0735

Gnomad4 NFE AF: 0.0562

Gnomad4 OTH AF: 0.0375

Alfa AF: 0.0484 Hom.: 149

Bravo AF: 0.0328

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.6
Dann	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs243144; hg19: chr14-63270121;