2-162679678-G-T

Variant names:

• chr2-162679678-G-T
• rs1435010
• NM_033272.4:c.308-142598C>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.308-142598C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 151,474 control chromosomes in the GnomAD database, including 1,497 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 0.13 (1497 hom., cov: 32)
• Consequence: KCNH7 NM_033272.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.756
• Publications: 1 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH7	NM_033272.4	c.308-142598C>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.308-142598C>A		intron_variant	Intron 2 of 15	1	NM_033272.4	ENSP00000331727.5
KCNH7	ENST00000328032.8	c.308-142598C>A		intron_variant	Intron 2 of 7	1		ENSP00000333781.4

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19840 AN: 151356 Hom.: 1499 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0989

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.131 AC: 19842 AN: 151474 Hom.: 1497 Cov.: 32 AF XY: 0.133 AC XY: 9814 AN XY: 74024

African (AFR) AF: 0.131 AC: 5428 AN: 41396

American (AMR) AF: 0.0987 AC: 1496 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 779 AN: 3462

East Asian (EAS) AF: 0.342 AC: 1754 AN: 5124

South Asian (SAS) AF: 0.180 AC: 866 AN: 4816

European-Finnish (FIN) AF: 0.123 AC: 1303 AN: 10574

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7806 AN: 67642

Other (OTH) AF: 0.130 AC: 273 AN: 2100

Alfa AF: 0.119 Hom.: 130

Bravo AF: 0.130

Asia WGS AF: 0.226 AC: 783 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.5
DANN	Benign	0.39
PhyloP100		0.76
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: rs1435010; hg19: chr2-163536188;