NM_001278919.2:c.675+260A>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278919.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH6	NM_001278919.2	MANE Select	c.675+260A>G		intron	N/A	NP_001265848.1
	KCNH6	NM_030779.4		c.675+260A>G		intron	N/A	NP_110406.1
	KCNH6	NM_173092.4		c.675+260A>G		intron	N/A	NP_775115.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH6	ENST00000314672.10	TSL:2 MANE Select	c.675+260A>G		intron	N/A	ENSP00000318212.5
	KCNH6	ENST00000583023.1	TSL:1	c.675+260A>G		intron	N/A	ENSP00000463533.1
	KCNH6	ENST00000580652.5	TSL:1	c.675+260A>G		intron	N/A	ENSP00000464672.1

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

African (AFR) AF: 0.301 AC: 12493 AN: 41480

American (AMR) AF: 0.329 AC: 5029 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1716 AN: 3472

East Asian (EAS) AF: 0.231 AC: 1192 AN: 5164

South Asian (SAS) AF: 0.278 AC: 1340 AN: 4818

European-Finnish (FIN) AF: 0.311 AC: 3291 AN: 10578

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23430 AN: 67932

Other (OTH) AF: 0.366 AC: 773 AN: 2110

Alfa AF: 0.350 Hom.: 1993

Bravo AF: 0.329

Asia WGS AF: 0.230 AC: 804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.29
DANN	Benign	0.51
PhyloP100		-1.9
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: rs11655589; hg19: chr17-61608163; COSMIC: COSV59008033;