rs4968656

Variant names:

• chr17-63539598-A-G
• rs4968656
• NM_001278919.2:c.1954+936A>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.1954+936A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,150 control chromosomes in the GnomAD database, including 6,064 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 0.26 (6064 hom., cov: 32)
• Consequence: KCNH6 NM_001278919.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 12 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]

ENSG00000307661 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH6	NM_001278919.2	c.1954+936A>G		intron_variant	Intron 8 of 12	ENST00000314672.10	NP_001265848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH6	ENST00000314672.10	c.1954+936A>G		intron_variant	Intron 8 of 12	2	NM_001278919.2	ENSP00000318212.5

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38813 AN: 152032 Hom.: 6063 Cov.: 32

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.255 AC: 38810 AN: 152150 Hom.: 6064 Cov.: 32 AF XY: 0.256 AC XY: 19016 AN XY: 74380

African (AFR) AF: 0.0721 AC: 2995 AN: 41530

American (AMR) AF: 0.301 AC: 4608 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1628 AN: 3468

East Asian (EAS) AF: 0.301 AC: 1555 AN: 5166

South Asian (SAS) AF: 0.278 AC: 1344 AN: 4828

European-Finnish (FIN) AF: 0.306 AC: 3239 AN: 10572

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22373 AN: 67962

Other (OTH) AF: 0.307 AC: 650 AN: 2114

Alfa AF: 0.318 Hom.: 13754

Bravo AF: 0.248

Asia WGS AF: 0.225 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.1
DANN	Benign	0.73
PhyloP100		0.11
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: rs4968656; hg19: chr17-61616959;