NM_033272.4:c.308-141573T>G

Variant names:

• chr2-162678653-A-C
• rs9287822
• NM_033272.4:c.308-141573T>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.308-141573T>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 151,382 control chromosomes in the GnomAD database, including 2,255 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 (2255 hom., cov: 32)
• Consequence: KCNH7 NM_033272.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.884
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033272.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH7	NM_033272.4	MANE Select	c.308-141573T>G		intron	N/A	NP_150375.2
	KCNH7	NM_173162.3		c.308-141573T>G		intron	N/A	NP_775185.1	Q9NS40-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH7	ENST00000332142.10	TSL:1 MANE Select	c.308-141573T>G		intron	N/A	ENSP00000331727.5	Q9NS40-1
	KCNH7	ENST00000328032.8	TSL:1	c.308-141573T>G		intron	N/A	ENSP00000333781.4	Q9NS40-2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24038 AN: 151266 Hom.: 2249 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.126

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: 0.148

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

GnomAD4 genome AF: 0.159 AC: 24056 AN: 151382 Hom.: 2255 Cov.: 32 AF XY: 0.163 AC XY: 12038 AN XY: 73992

African (AFR) AF: 0.154 AC: 6383 AN: 41418

American (AMR) AF: 0.126 AC: 1914 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 875 AN: 3452

East Asian (EAS) AF: 0.458 AC: 2347 AN: 5124

South Asian (SAS) AF: 0.241 AC: 1159 AN: 4808

European-Finnish (FIN) AF: 0.172 AC: 1822 AN: 10574

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

European-Non Finnish (NFE) AF: 0.135 AC: 9085 AN: 67536

Other (OTH) AF: 0.151 AC: 319 AN: 2106

Alfa AF: 0.136 Hom.: 236

Bravo AF: 0.156

Asia WGS AF: 0.323 AC: 1123 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.55
PhyloP100		0.88
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: rs9287822; hg19: chr2-163535163;