chr2-162813784-C-T

Variant names:

• chr2-162813784-C-T
• rs3843856
• NM_033272.4:c.307+22753G>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.307+22753G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 152,250 control chromosomes in the GnomAD database, including 67,486 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 0.94 (67486 hom., cov: 32)
• Consequence: KCNH7 NM_033272.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.430
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH7	NM_033272.4	c.307+22753G>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.307+22753G>A		intron_variant	Intron 2 of 15	1	NM_033272.4	ENSP00000331727.5
KCNH7	ENST00000328032.8	c.307+22753G>A		intron_variant	Intron 2 of 7	1		ENSP00000333781.4

Frequencies

GnomAD3 genomes AF: 0.941 AC: 143114 AN: 152130 Hom.: 67436 Cov.: 32

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.966

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.963

Gnomad OTH AF: 0.963

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

GnomAD4 genome AF: 0.941 AC: 143224 AN: 152250 Hom.: 67486 Cov.: 32 AF XY: 0.942 AC XY: 70116 AN XY: 74418

African (AFR) AF: 0.881 AC: 36584 AN: 41518

American (AMR) AF: 0.967 AC: 14792 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3456 AN: 3472

East Asian (EAS) AF: 0.914 AC: 4731 AN: 5174

South Asian (SAS) AF: 0.967 AC: 4669 AN: 4830

European-Finnish (FIN) AF: 0.968 AC: 10271 AN: 10612

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.963 AC: 65521 AN: 68030

Other (OTH) AF: 0.963 AC: 2038 AN: 2116

Alfa AF: 0.943 Hom.: 9135

Bravo AF: 0.937

Asia WGS AF: 0.937 AC: 3258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.22
PhyloP100		0.43
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: rs3843856; hg19: chr2-163670294; COSMIC: COSV59811293;