rs4968656

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.111
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons MANE UniProt
KCNH6NM_001278919.2 linkuse as main transcriptc.1954+936A>G intron_variant ENST00000314672.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KCNH6ENST00000314672.10 linkuse as main transcriptc.1954+936A>G intron_variant 2 NM_001278919.2 P1

Frequencies

GnomAD3 genomes
AF:
0.255
AC:
38813
AN:
152032
Hom.:
6063
Cov.:
32
show subpopulations
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
show subpopulations
Gnomad4 AFR
AF:
0.0721
Gnomad4 AMR
AF:
0.301
Gnomad4 ASJ
AF:
0.469
Gnomad4 EAS
AF:
0.301
Gnomad4 SAS
AF:
0.278
Gnomad4 FIN
AF:
0.306
Gnomad4 NFE
AF:
0.329
Gnomad4 OTH
AF:
0.307
Alfa
AF:
0.328
Hom.:
11318
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

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4968656; hg19: chr17-61616959; API