rs1934614

Variant names:

• chr1-210794870-T-A
• rs1934614
• NM_172362.3:c.1915+2638A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-210794870-T-A
• chr1-210794870-T-C

Variant summary

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

The NM_172362.3(KCNH1):​c.1915+2638A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,106 control chromosomes in the GnomAD database, including 6,267 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 0.26 (6267 hom., cov: 32)
• Consequence: KCNH1 NM_172362.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH1	NM_172362.3	c.1915+2638A>T		intron_variant	Intron 9 of 10	ENST00000271751.10	NP_758872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH1	ENST00000271751.10	c.1915+2638A>T		intron_variant	Intron 9 of 10	2	NM_172362.3	ENSP00000271751.4

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38760 AN: 151988 Hom.: 6239 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.255 AC: 38851 AN: 152106 Hom.: 6267 Cov.: 32 AF XY: 0.252 AC XY: 18730 AN XY: 74360

African (AFR) AF: 0.465 AC: 19271 AN: 41454

American (AMR) AF: 0.220 AC: 3358 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 573 AN: 3470

East Asian (EAS) AF: 0.173 AC: 897 AN: 5184

South Asian (SAS) AF: 0.144 AC: 693 AN: 4814

European-Finnish (FIN) AF: 0.193 AC: 2046 AN: 10588

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11447 AN: 67992

Other (OTH) AF: 0.219 AC: 464 AN: 2116

Alfa AF: 0.214 Hom.: 532

Bravo AF: 0.263

Asia WGS AF: 0.196 AC: 684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.8
DANN	Benign	0.43
PhyloP100		0.36
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: rs1934614; hg19: chr1-210968212; COSMIC: COSV55106431;