chr1-210995417-G-A

Position:

• chr1-210995417-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH1	NM_172362.3	c.1032+23366C>T		intron_variant		ENST00000271751.10	NP_758872.1
KCNH1	NM_002238.4	c.951+23447C>T		intron_variant			NP_002229.1
KCNH1	XM_047419823.1	c.951+23447C>T		intron_variant			XP_047275779.1
KCNH1	XM_047419829.1	c.-51+23447C>T		intron_variant			XP_047275785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNH1	ENST00000271751.10	c.1032+23366C>T		intron_variant		2	NM_172362.3	ENSP00000271751

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

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.0803

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.243

Alfa AF: 0.204 Hom.: 706

Bravo AF: 0.262

Asia WGS AF: 0.253 AC: 879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.5
DANN	Benign	0.59

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: rs1501550; hg19: chr1-211168759;