rs1435013

Variant names:

• chr2-162669601-A-C
• rs1435013
• NM_033272.4:c.308-132521T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-162669601-A-C
• chr2-162669601-A-G

Variant summary

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

The NM_033272.4(KCNH7):​c.308-132521T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,154 control chromosomes in the GnomAD database, including 2,258 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 0.16 (2258 hom., cov: 32)
• Consequence: KCNH7 NM_033272.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• Publications: 2 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH7	NM_033272.4	c.308-132521T>G		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.308-132521T>G		intron_variant	Intron 2 of 15	1	NM_033272.4	ENSP00000331727.5
KCNH7	ENST00000328032.8	c.308-132521T>G		intron_variant	Intron 2 of 7	1		ENSP00000333781.4

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24160 AN: 152036 Hom.: 2252 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.159 AC: 24179 AN: 152154 Hom.: 2258 Cov.: 32 AF XY: 0.163 AC XY: 12103 AN XY: 74378

African (AFR) AF: 0.154 AC: 6401 AN: 41514

American (AMR) AF: 0.126 AC: 1933 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 879 AN: 3470

East Asian (EAS) AF: 0.458 AC: 2363 AN: 5162

South Asian (SAS) AF: 0.241 AC: 1163 AN: 4828

European-Finnish (FIN) AF: 0.172 AC: 1818 AN: 10582

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9148 AN: 67994

Other (OTH) AF: 0.152 AC: 322 AN: 2114

Alfa AF: 0.129 Hom.: 736

Bravo AF: 0.156

Asia WGS AF: 0.324 AC: 1126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.53
DANN	Benign	0.63
PhyloP100		-2.0
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: rs1435013; hg19: chr2-163526111;