3-19334299-G-A

Variant names:

• chr3-19334299-G-A
• rs2053506
• NM_144633.3:c.443-8288G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KCNH8	NM_144633.3	c.443-8288G>A		intron_variant	Intron 3 of 15	ENST00000328405.7	NP_653234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH8	ENST00000328405.7	c.443-8288G>A		intron_variant	Intron 3 of 15	1	NM_144633.3	ENSP00000328813.2
KCNH8	ENST00000452398.5	n.443-8288G>A		intron_variant	Intron 3 of 15	1		ENSP00000412141.1

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

African (AFR) AF: 0.888 AC: 36834 AN: 41486

American (AMR) AF: 0.711 AC: 10832 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2187 AN: 3466

East Asian (EAS) AF: 0.861 AC: 4431 AN: 5146

South Asian (SAS) AF: 0.769 AC: 3704 AN: 4814

European-Finnish (FIN) AF: 0.615 AC: 6500 AN: 10564

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.621 AC: 42192 AN: 67946

Other (OTH) AF: 0.716 AC: 1513 AN: 2112

Alfa AF: 0.661 Hom.: 144839

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
PhyloP100		-5.1
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: rs2053506; hg19: chr3-19375791;