Variant 1-210683262-T-G 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.*19A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 1,604,628 control chromosomes in the GnomAD database, including 3,769 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 265 hom., cov: 32)

Exomes 𝑓: 0.066 ( 3504 hom. )

Consequence

KCNH1
NM_172362.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.493

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=-0.81).

BP6

Variant 1-210683262-T-G is Benign according to our data. Variant chr1-210683262-T-G is described in ClinVar as [Benign]. Clinvar id is 1277290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0722 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.*19A>C		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.*19A>C		3_prime_UTR_variant	11/11	2	NM_172362.3	ENSP00000271751.4		O95259-1

Frequencies

GnomAD3 genomes

AF:

0.0485

AC:

7357

AN:

151752

Hom.:

265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0127

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.0583

Gnomad ASJ

AF:

0.0497

Gnomad EAS

AF:

0.000581

Gnomad SAS

AF:

0.0489

Gnomad FIN

AF:

0.0343

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0738

Gnomad OTH

AF:

0.0619

GnomAD3 exomes

AF:

0.0561

AC:

13239

AN:

236192

Hom.:

483

AF XY:

0.0586

AC XY:

7504

AN XY:

128090

show subpopulations

Gnomad AFR exome

AF:

0.0110

Gnomad AMR exome

AF:

0.0437

Gnomad ASJ exome

AF:

0.0581

Gnomad EAS exome

AF:

0.000393

Gnomad SAS exome

AF:

0.0560

Gnomad FIN exome

AF:

0.0382

Gnomad NFE exome

AF:

0.0773

Gnomad OTH exome

AF:

0.0727

GnomAD4 exome

AF:

0.0662

AC:

96153

AN:

1452758

Hom.:

3504

Cov.:

AF XY:

0.0661

AC XY:

47697

AN XY:

722020

show subpopulations

Gnomad4 AFR exome

AF:

0.0111

Gnomad4 AMR exome

AF:

0.0444

Gnomad4 ASJ exome

AF:

0.0509

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.0500

Gnomad4 FIN exome

AF:

0.0358

Gnomad4 NFE exome

AF:

0.0742

Gnomad4 OTH exome

AF:

0.0609

GnomAD4 genome

AF:

0.0484

AC:

7358

AN:

151870

Hom.:

265

Cov.:

AF XY:

0.0480

AC XY:

3564

AN XY:

74210

show subpopulations

Gnomad4 AFR

AF:

0.0127

Gnomad4 AMR

AF:

0.0582

Gnomad4 ASJ

AF:

0.0497

Gnomad4 EAS

AF:

0.000583

Gnomad4 SAS

AF:

0.0489

Gnomad4 FIN

AF:

0.0343

Gnomad4 NFE

AF:

0.0739

Gnomad4 OTH

AF:

0.0613

Alfa

AF:

0.0661

Hom.:

Bravo

AF:

0.0488

Asia WGS

AF:

0.0340

AC:

117

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	clinical testing	GeneDx	Jul 17, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.55

DANN

Benign

0.64

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