rs1418973

Variant names:

• chr1-210820997-G-A
• rs1418973
• NM_172362.3:c.1463-16831C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-210820997-G-A
• chr1-210820997-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172362.3(KCNH1):​c.1463-16831C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,110 control chromosomes in the GnomAD database, including 34,477 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (34477 hom., cov: 32)
• Consequence: KCNH1 NM_172362.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• KCNH1 associated disorder

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Illumina
• Temple-Baraitser syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
• Zimmermann-Laband syndrome 1

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• Zimmermann-Laband syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH1	NM_172362.3	c.1463-16831C>T		intron_variant	Intron 7 of 10	ENST00000271751.10	NP_758872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH1	ENST00000271751.10	c.1463-16831C>T		intron_variant	Intron 7 of 10	2	NM_172362.3	ENSP00000271751.4

Frequencies

GnomAD3 genomes AF: 0.671 AC: 102046 AN: 151992 Hom.: 34450 Cov.: 32

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.661

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.671 AC: 102117 AN: 152110 Hom.: 34477 Cov.: 32 AF XY: 0.674 AC XY: 50101 AN XY: 74336

African (AFR) AF: 0.610 AC: 25314 AN: 41480

American (AMR) AF: 0.605 AC: 9256 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2341 AN: 3472

East Asian (EAS) AF: 0.784 AC: 4047 AN: 5164

South Asian (SAS) AF: 0.718 AC: 3461 AN: 4818

European-Finnish (FIN) AF: 0.738 AC: 7809 AN: 10578

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47771 AN: 67990

Other (OTH) AF: 0.664 AC: 1402 AN: 2112

Alfa AF: 0.685 Hom.: 112189

Bravo AF: 0.656

Asia WGS AF: 0.752 AC: 2615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.58
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1418973; hg19: chr1-210994339;