2-162832888-C-T

Position:

• chr2-162832888-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KCNH7	NM_033272.4	c.307+3649G>A		intron_variant		ENST00000332142.10	NP_150375.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNH7	ENST00000332142.10	c.307+3649G>A		intron_variant		1	NM_033272.4	ENSP00000331727	P1
KCNH7	ENST00000328032.8	c.307+3649G>A		intron_variant		1		ENSP00000333781

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

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.729

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.533

Alfa AF: 0.569 Hom.: 4023

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

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: rs4667468; hg19: chr2-163689398;