chr2-162384337-T-G

Variant names:

• chr2-162384337-T-G
• rs1549020
• NM_033272.4:c.2962+351A>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.2962+351A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,620 control chromosomes in the GnomAD database, including 16,677 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 0.43 (16677 hom., cov: 31)
• Consequence: KCNH7 NM_033272.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 14 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.808 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.2962+351A>C		intron	N/A	NP_150375.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH7	ENST00000332142.10	TSL:1 MANE Select	c.2962+351A>C		intron	N/A	ENSP00000331727.5	Q9NS40-1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64543 AN: 151504 Hom.: 16629 Cov.: 31

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.426 AC: 64650 AN: 151620 Hom.: 16677 Cov.: 31 AF XY: 0.432 AC XY: 32002 AN XY: 74072

African (AFR) AF: 0.685 AC: 28358 AN: 41398

American (AMR) AF: 0.403 AC: 6116 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1044 AN: 3460

East Asian (EAS) AF: 0.829 AC: 4247 AN: 5124

South Asian (SAS) AF: 0.416 AC: 2004 AN: 4812

European-Finnish (FIN) AF: 0.344 AC: 3633 AN: 10568

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18096 AN: 67776

Other (OTH) AF: 0.375 AC: 789 AN: 2106

Alfa AF: 0.301 Hom.: 9007

Bravo AF: 0.444

Asia WGS AF: 0.602 AC: 2088 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.51
PhyloP100		0.021
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: rs1549020; hg19: chr2-163240847;