rs2053506

chr3-19334299-G-Achr3-19334299-G-C

Variant summary

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

The NM_144633.3(KCNH8):c.443-8288G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 151,976 control chromosomes in the GnomAD database, including 40,281 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 0.72 (40281 hom., cov: 30)
• Consequence: KCNH8 NM_144633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.08

Genes affected

KCNH8 (HGNC:18864): (potassium voltage-gated channel subfamily H member 8) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, subfamily H. This member is a pore-forming (alpha) subunit. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.08).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNH8	NM_144633.3	c.443-8288G>A		intron_variant		ENST00000328405.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNH8	ENST00000328405.7	c.443-8288G>A		intron_variant		1	NM_144633.3	P1
KCNH8	ENST00000452398.5	c.443-8288G>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109085 AN: 151858 Hom.: 40221 Cov.: 30

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.719 AC: 109201 AN: 151976 Hom.: 40281 Cov.: 30 AF XY: 0.720 AC XY: 53468 AN XY: 74288

Gnomad4 AFR AF: 0.888

Gnomad4 AMR AF: 0.711

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.861

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.716

Alfa AF: 0.649 Hom.: 67857

Bravo AF: 0.738

Asia WGS AF: 0.805 AC: 2800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.44
Dann	Benign	0.58

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: rs2053506; hg19: chr3-19375791;