1-210683243-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.561

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
KCNH1	NM_172362.3	c.*38C>A		3_prime_UTR_variant	11/11	ENST00000271751.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNH1	ENST00000271751.10	c.*38C>A		3_prime_UTR_variant	11/11	2	NM_172362.3

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111824 AN: 151750 Hom.: 41888 Cov.: 30

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

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.: 30 AF XY: 0.707 AC XY: 501759 AN XY: 710022

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.: 30 AF XY: 0.735 AC XY: 54557 AN XY: 74212

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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

Other links and lift over

dbSNP: rs3135473; hg19: chr1-210856585; COSMIC: COSV55073654; COSMIC: COSV55073654;