rs10497229

Variant names:

• chr2-162835048-A-G
• rs10497229
• NM_033272.4:c.307+1489T>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.307+1489T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 152,210 control chromosomes in the GnomAD database, including 839 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 0.076 (839 hom., cov: 32)
• Consequence: KCNH7 NM_033272.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH7	NM_033272.4	c.307+1489T>C		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+1489T>C		intron_variant	Intron 2 of 15	1	NM_033272.4	ENSP00000331727.5
KCNH7	ENST00000328032.8	c.307+1489T>C		intron_variant	Intron 2 of 7	1		ENSP00000333781.4

Frequencies

GnomAD3 genomes AF: 0.0757 AC: 11518 AN: 152092 Hom.: 835 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0396

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.0430

Gnomad SAS AF: 0.0250

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0318

Gnomad OTH AF: 0.0675

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

GnomAD4 genome AF: 0.0758 AC: 11542 AN: 152210 Hom.: 839 Cov.: 32 AF XY: 0.0732 AC XY: 5451 AN XY: 74426

African (AFR) AF: 0.190 AC: 7888 AN: 41532

American (AMR) AF: 0.0396 AC: 605 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 197 AN: 3468

East Asian (EAS) AF: 0.0428 AC: 222 AN: 5192

South Asian (SAS) AF: 0.0248 AC: 120 AN: 4832

European-Finnish (FIN) AF: 0.0112 AC: 119 AN: 10618

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0318 AC: 2164 AN: 67960

Other (OTH) AF: 0.0668 AC: 141 AN: 2112

Alfa AF: 0.0524 Hom.: 150

Bravo AF: 0.0838

Asia WGS AF: 0.0510 AC: 178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.7
DANN	Benign	0.38
PhyloP100		1.5
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: rs10497229; hg19: chr2-163691558;