1-210683262-T-G

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.*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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.493

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=-0.81).
• 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_single_submitter, 1 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	UniProt
KCNH1	NM_172362.3	c.*19A>C		3_prime_UTR_variant	11/11	ENST00000271751.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNH1	ENST00000271751.10	c.*19A>C		3_prime_UTR_variant	11/11	2	NM_172362.3

Frequencies

GnomAD3 genomes AF: 0.0485 AC: 7357 AN: 151752 Hom.: 265 Cov.: 32

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

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.: 36 AF XY: 0.0661 AC XY: 47697 AN XY: 722020

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.: 32 AF XY: 0.0480 AC XY: 3564 AN XY: 74210

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.: 98

Bravo AF: 0.0488

Asia WGS AF: 0.0340 AC: 117 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 17, 2018

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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

Other links and lift over

dbSNP: rs34689382; hg19: chr1-210856604;