chr2-162404181-T-C

Variant names:

• chr2-162404181-T-C
• rs17716942
• NM_033272.4:c.2155-3740A>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.2155-3740A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 151,940 control chromosomes in the GnomAD database, including 942 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 0.095 (942 hom., cov: 32)
• Consequence: KCNH7 NM_033272.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412
• Publications: 54 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.137 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH7	NM_033272.4	MANE Select	c.2155-3740A>G		intron	N/A	NP_150375.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH7	ENST00000332142.10	TSL:1 MANE Select	c.2155-3740A>G		intron	N/A	ENSP00000331727.5

Frequencies

GnomAD3 genomes AF: 0.0955 AC: 14499 AN: 151822 Hom.: 942 Cov.: 32

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.0956

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.00156

Gnomad SAS AF: 0.0528

Gnomad FIN AF: 0.0997

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.0954 AC: 14494 AN: 151940 Hom.: 942 Cov.: 32 AF XY: 0.0934 AC XY: 6934 AN XY: 74226

African (AFR) AF: 0.0260 AC: 1079 AN: 41504

American (AMR) AF: 0.0954 AC: 1455 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 776 AN: 3466

East Asian (EAS) AF: 0.00156 AC: 8 AN: 5114

South Asian (SAS) AF: 0.0529 AC: 255 AN: 4822

European-Finnish (FIN) AF: 0.0997 AC: 1056 AN: 10592

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9472 AN: 67878

Other (OTH) AF: 0.115 AC: 242 AN: 2110

Alfa AF: 0.125 Hom.: 4729

Bravo AF: 0.0919

Asia WGS AF: 0.0310 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.97
DANN	Benign	0.49
PhyloP100		-0.41
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: rs17716942; hg19: chr2-163260691;