rs243146

chr14-62838427-A-Gchr14-62838427-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	UniProt
KCNH5	NM_139318.5	c.1569+11226T>C		intron_variant		ENST00000322893.12
KCNH5	NM_172375.3	c.1569+11226T>C		intron_variant
KCNH5	XM_047431275.1	c.1569+11226T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNH5	ENST00000322893.12	c.1569+11226T>C		intron_variant		1	NM_139318.5	P1
KCNH5	ENST00000420622.6	c.1569+11226T>C		intron_variant		1
KCNH5	ENST00000394968.2	c.1395+11226T>C		intron_variant		2

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

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.330

Alfa AF: 0.315 Hom.: 1234

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

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: rs243146; hg19: chr14-63305145;