rs11655589

Variant names:

• chr17-63530802-A-G
• rs11655589
• NM_001278919.2:c.675+260A>G

Variant summary

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

The NM_001278919.2(KCNH6):​c.675+260A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,048 control chromosomes in the GnomAD database, including 8,312 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 0.33 (8312 hom., cov: 33)
• Consequence: KCNH6 NM_001278919.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

Genes affected

KCNH6 (HGNC:18862): (potassium voltage-gated channel subfamily H member 6) 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. Alternative splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH6	NM_001278919.2	c.675+260A>G		intron_variant	Intron 4 of 12	ENST00000314672.10	NP_001265848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH6	ENST00000314672.10	c.675+260A>G		intron_variant	Intron 4 of 12	2	NM_001278919.2	ENSP00000318212.5

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49715 AN: 151930 Hom.: 8308 Cov.: 33

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.327 AC: 49744 AN: 152048 Hom.: 8312 Cov.: 33 AF XY: 0.326 AC XY: 24225 AN XY: 74332

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.366

Alfa AF: 0.351 Hom.: 1947

Bravo AF: 0.329

Asia WGS AF: 0.230 AC: 804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.29
DANN	Benign	0.51

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: rs11655589; hg19: chr17-61608163; COSMIC: COSV59008033;