chr2-162832888-C-T

Variant names:

• chr2-162832888-C-T
• rs4667468
• NM_033272.4:c.307+3649G>A

Variant summary

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

The NM_033272.4(KCNH7):​c.307+3649G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,846 control chromosomes in the GnomAD database, including 22,216 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 0.53 (22216 hom., cov: 32)
• Consequence: KCNH7 NM_033272.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH7	NM_033272.4	c.307+3649G>A		intron_variant	Intron 2 of 15	ENST00000332142.10	NP_150375.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH7	ENST00000332142.10	c.307+3649G>A		intron_variant	Intron 2 of 15	1	NM_033272.4	ENSP00000331727.5
KCNH7	ENST00000328032.8	c.307+3649G>A		intron_variant	Intron 2 of 7	1		ENSP00000333781.4

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80354 AN: 151726 Hom.: 22206 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.529 AC: 80396 AN: 151846 Hom.: 22216 Cov.: 32 AF XY: 0.530 AC XY: 39368 AN XY: 74210

African (AFR) AF: 0.360 AC: 14888 AN: 41398

American (AMR) AF: 0.538 AC: 8204 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1941 AN: 3464

East Asian (EAS) AF: 0.586 AC: 3022 AN: 5160

South Asian (SAS) AF: 0.729 AC: 3513 AN: 4820

European-Finnish (FIN) AF: 0.515 AC: 5430 AN: 10540

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41581 AN: 67908

Other (OTH) AF: 0.533 AC: 1120 AN: 2102

Alfa AF: 0.562 Hom.: 4077

Bravo AF: 0.513

Asia WGS AF: 0.623 AC: 2166 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.20
PhyloP100		-0.55
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: rs4667468; hg19: chr2-163689398;