Variant chr1-211103486-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_172362.3(KCNH1):c.310+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,523,160 control chromosomes in the GnomAD database, including 37,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3037 hom., cov: 33)

Exomes 𝑓: 0.22 ( 34341 hom. )

Consequence

KCNH1
NM_172362.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.639

Variant links:

Genes affected

KCNH1 (HGNC:6250): (potassium voltage-gated channel subfamily H member 1) 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 of a voltage-gated non-inactivating delayed rectifier potassium channel. It is activated at the onset of myoblast differentiation. The gene is highly expressed in brain and in myoblasts. Overexpression of the gene may confer a growth advantage to cancer cells and favor tumor cell proliferation. Alternative splicing of this gene results in two transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

KCNH1 links:

ENSG00000283952 (HGNC:):

ENSG00000283952 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 1-211103486-C-T is Benign according to our data. Variant chr1-211103486-C-T is described in ClinVar as [Benign]. Clinvar id is 262807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
KCNH1	NM_172362.3 linkuse as main transcript	c.310+10G>A	intron_variant	ENST00000271751.10	NP_758872.1	O95259-1
KCNH1	NM_002238.4 linkuse as main transcript	c.310+10G>A	intron_variant		NP_002229.1	O95259-2
KCNH1	XM_047419823.1 linkuse as main transcript	c.310+10G>A	intron_variant		XP_047275779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNH1	ENST00000271751.10 linkuse as main transcript	c.310+10G>A		intron_variant		2	NM_172362.3	ENSP00000271751.4		O95259-1
ENSG00000283952	ENST00000638880.1 linkuse as main transcript	c.130+10G>A		intron_variant		5		ENSP00000491750.1		A0A1W2PPV4

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29165

AN:

152056

Hom.:

3037

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.139

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.241

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.196

GnomAD3 exomes

AF:

0.189

AC:

46772

AN:

247452

Hom.:

4940

AF XY:

0.193

AC XY:

25807

AN XY:

133712

show subpopulations

Gnomad AFR exome

AF:

0.139

Gnomad AMR exome

AF:

0.106

Gnomad ASJ exome

AF:

0.247

Gnomad EAS exome

AF:

0.120

Gnomad SAS exome

AF:

0.149

Gnomad FIN exome

AF:

0.230

Gnomad NFE exome

AF:

0.230

Gnomad OTH exome

AF:

0.202

GnomAD4 exome

AF:

0.218

AC:

298787

AN:

1370986

Hom.:

34341

Cov.:

AF XY:

0.217

AC XY:

149011

AN XY:

686952

show subpopulations

Gnomad4 AFR exome

AF:

0.143

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.250

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.158

Gnomad4 FIN exome

AF:

0.229

Gnomad4 NFE exome

AF:

0.233

Gnomad4 OTH exome

AF:

0.212

GnomAD4 genome

AF:

0.192

AC:

29171

AN:

152174

Hom.:

3037

Cov.:

AF XY:

0.191

AC XY:

14229

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.147

Gnomad4 ASJ

AF:

0.251

Gnomad4 EAS

AF:

0.112

Gnomad4 SAS

AF:

0.150

Gnomad4 FIN

AF:

0.241

Gnomad4 NFE

AF:

0.230

Gnomad4 OTH

AF:

0.194

Alfa

AF:

0.214

Hom.:

4146

Bravo

AF:

0.183

Asia WGS

AF:

0.119

AC:

411

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.8

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over