rs12185647

Variant names:

• chr2-162551742-A-G
• rs12185647
• NM_033272.4:c.308-14662T>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.308-14662T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,046 control chromosomes in the GnomAD database, including 9,500 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 0.31 (9500 hom., cov: 32)
• Consequence: KCNH7 NM_033272.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.773
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH7	NM_033272.4	c.308-14662T>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.308-14662T>C		intron_variant	Intron 2 of 15	1	NM_033272.4	ENSP00000331727.5
KCNH7	ENST00000328032.8	c.308-14662T>C		intron_variant	Intron 2 of 7	1		ENSP00000333781.4

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46828 AN: 151928 Hom.: 9509 Cov.: 32

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.00733

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.308 AC: 46807 AN: 152046 Hom.: 9500 Cov.: 32 AF XY: 0.299 AC XY: 22205 AN XY: 74314

African (AFR) AF: 0.0823 AC: 3417 AN: 41518

American (AMR) AF: 0.286 AC: 4366 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1287 AN: 3466

East Asian (EAS) AF: 0.00734 AC: 38 AN: 5174

South Asian (SAS) AF: 0.198 AC: 952 AN: 4814

European-Finnish (FIN) AF: 0.378 AC: 3990 AN: 10544

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.464 AC: 31532 AN: 67948

Other (OTH) AF: 0.337 AC: 712 AN: 2110

Alfa AF: 0.389 Hom.: 10902

Bravo AF: 0.290

Asia WGS AF: 0.107 AC: 373 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.1
DANN	Benign	0.86
PhyloP100		0.77
Mutation Taster		=99/1	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: rs12185647; hg19: chr2-163408252;