rs2068330

Variant names:

• chr2-162380880-C-G
• rs2068330
• NM_033272.4:c.2963-859G>C

Variant summary

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

The NM_033272.4(KCNH7):​c.2963-859G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 151,842 control chromosomes in the GnomAD database, including 20,228 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 0.49 (20228 hom., cov: 31)
• Consequence: KCNH7 NM_033272.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335
• Publications: 18 publications found

Genes affected

KCNH7 (HGNC:18863): (potassium voltage-gated channel subfamily H member 7) 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. There are at least two alternatively spliced transcript variants derived from this gene and encoding distinct isoforms. [provided by RefSeq, Jul 2008]

KCNH7 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033272.4. 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
	KCNH7	NM_033272.4	MANE Select	c.2963-859G>C		intron	N/A	NP_150375.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH7	ENST00000332142.10	TSL:1 MANE Select	c.2963-859G>C		intron	N/A	ENSP00000331727.5	Q9NS40-1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74316 AN: 151724 Hom.: 20178 Cov.: 31

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.490 AC: 74423 AN: 151842 Hom.: 20228 Cov.: 31 AF XY: 0.495 AC XY: 36688 AN XY: 74184

African (AFR) AF: 0.703 AC: 29101 AN: 41420

American (AMR) AF: 0.470 AC: 7150 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1713 AN: 3466

East Asian (EAS) AF: 0.825 AC: 4245 AN: 5148

South Asian (SAS) AF: 0.451 AC: 2170 AN: 4816

European-Finnish (FIN) AF: 0.403 AC: 4244 AN: 10534

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24331 AN: 67924

Other (OTH) AF: 0.461 AC: 973 AN: 2110

Alfa AF: 0.426 Hom.: 1893

Bravo AF: 0.507

Asia WGS AF: 0.620 AC: 2151 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.42
DANN	Benign	0.62
PhyloP100		-0.34
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: rs2068330; hg19: chr2-163237390;