rs1501550

Variant names:

• chr1-210995417-G-A
• rs1501550
• NM_172362.3:c.1032+23366C>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.1032+23366C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 151,902 control chromosomes in the GnomAD database, including 5,887 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 0.24 (5887 hom., cov: 32)
• Consequence: KCNH1 NM_172362.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367
• Publications: 5 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: Illumina, ClinGen
• Temple-Baraitser syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172362.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH1	NM_172362.3	MANE Select	c.1032+23366C>T		intron	N/A	NP_758872.1	O95259-1
	KCNH1	NM_002238.4		c.951+23447C>T		intron	N/A	NP_002229.1	O95259-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH1	ENST00000271751.10	TSL:2 MANE Select	c.1032+23366C>T		intron	N/A	ENSP00000271751.4	O95259-1
	KCNH1	ENST00000639952.1	TSL:1	c.951+23447C>T		intron	N/A	ENSP00000492697.1	O95259-2
	KCNH1	ENST00000640044.1	TSL:1	c.310+108079C>T		intron	N/A	ENSP00000491434.1	A0A1W2PPA2

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36053 AN: 151782 Hom.: 5868 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.0803

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.238 AC: 36120 AN: 151902 Hom.: 5887 Cov.: 32 AF XY: 0.235 AC XY: 17420 AN XY: 74238

African (AFR) AF: 0.448 AC: 18542 AN: 41386

American (AMR) AF: 0.234 AC: 3567 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 527 AN: 3464

East Asian (EAS) AF: 0.386 AC: 1992 AN: 5160

South Asian (SAS) AF: 0.181 AC: 871 AN: 4808

European-Finnish (FIN) AF: 0.0803 AC: 847 AN: 10550

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.133 AC: 9065 AN: 67952

Other (OTH) AF: 0.243 AC: 514 AN: 2112

Alfa AF: 0.254 Hom.: 3673

Bravo AF: 0.262

Asia WGS AF: 0.253 AC: 879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.5
DANN	Benign	0.59
PhyloP100		-0.37
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: rs1501550; hg19: chr1-211168759;