Variant 1-210683243-G-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.*38C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 1,582,776 control chromosomes in the GnomAD database, including 398,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 41927 hom., cov: 30)

Exomes 𝑓: 0.70 ( 356561 hom. )

Consequence

KCNH1
NM_172362.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.561

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 1-210683243-G-T is Benign according to our data. Variant chr1-210683243-G-T is described in ClinVar as [Benign]. Clinvar id is 1276318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH1	NM_172362.3 linkuse as main transcript	c.*38C>A		3_prime_UTR_variant	11/11	ENST00000271751.10	NP_758872.1	O95259-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNH1	ENST00000271751 linkuse as main transcript	c.*38C>A		3_prime_UTR_variant	11/11	2	NM_172362.3	ENSP00000271751.4		O95259-1

Frequencies

GnomAD3 genomes

AF:

0.737

AC:

111824

AN:

151750

Hom.:

41888

Cov.:

show subpopulations

Gnomad AFR

AF:

0.854

Gnomad AMI

AF:

0.831

Gnomad AMR

AF:

0.716

Gnomad ASJ

AF:

0.796

Gnomad EAS

AF:

0.646

Gnomad SAS

AF:

0.806

Gnomad FIN

AF:

0.585

Gnomad MID

AF:

0.782

Gnomad NFE

AF:

0.691

Gnomad OTH

AF:

0.747

GnomAD3 exomes

AF:

0.706

AC:

164345

AN:

232850

Hom.:

58623

AF XY:

0.712

AC XY:

90026

AN XY:

126454

show subpopulations

Gnomad AFR exome

AF:

0.857

Gnomad AMR exome

AF:

0.647

Gnomad ASJ exome

AF:

0.802

Gnomad EAS exome

AF:

0.649

Gnomad SAS exome

AF:

0.806

Gnomad FIN exome

AF:

0.594

Gnomad NFE exome

AF:

0.698

Gnomad OTH exome

AF:

0.723

GnomAD4 exome

AF:

0.704

AC:

1006820

AN:

1430908

Hom.:

356561

Cov.:

AF XY:

0.707

AC XY:

501759

AN XY:

710022

show subpopulations

Gnomad4 AFR exome

AF:

0.866

Gnomad4 AMR exome

AF:

0.654

Gnomad4 ASJ exome

AF:

0.802

Gnomad4 EAS exome

AF:

0.644

Gnomad4 SAS exome

AF:

0.802

Gnomad4 FIN exome

AF:

0.591

Gnomad4 NFE exome

AF:

0.697

Gnomad4 OTH exome

AF:

0.719

GnomAD4 genome

AF:

0.737

AC:

111921

AN:

151868

Hom.:

41927

Cov.:

AF XY:

0.735

AC XY:

54557

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.854

Gnomad4 AMR

AF:

0.715

Gnomad4 ASJ

AF:

0.796

Gnomad4 EAS

AF:

0.645

Gnomad4 SAS

AF:

0.805

Gnomad4 FIN

AF:

0.585

Gnomad4 NFE

AF:

0.691

Gnomad4 OTH

AF:

0.749

Alfa

AF:

0.712

Hom.:

13952

Bravo

AF:

0.749

Asia WGS

AF:

0.751

AC:

2608

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.13

DANN

Benign

0.44

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