2-162782597-G-A

Variant names:

• chr2-162782597-G-A
• rs1032412
• NM_033272.4:c.307+53940C>T

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+53940C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,978 control chromosomes in the GnomAD database, including 25,279 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 0.54 (25279 hom., cov: 31)
• Consequence: KCNH7 NM_033272.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750
• Publications: 10 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-AS1 (HGNC:40858): (KCNH7 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.699 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.307+53940C>T		intron	N/A	NP_150375.2
	KCNH7	NM_173162.3		c.307+53940C>T		intron	N/A	NP_775185.1
	KCNH7-AS1	NR_110258.2		n.115-2000G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH7	ENST00000332142.10	TSL:1 MANE Select	c.307+53940C>T		intron	N/A	ENSP00000331727.5
	KCNH7	ENST00000328032.8	TSL:1	c.307+53940C>T		intron	N/A	ENSP00000333781.4
	KCNH7-AS1	ENST00000446838.2	TSL:1	n.115-2000G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81350 AN: 151862 Hom.: 25282 Cov.: 31

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.691

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.535 AC: 81353 AN: 151978 Hom.: 25279 Cov.: 31 AF XY: 0.533 AC XY: 39600 AN XY: 74274

African (AFR) AF: 0.209 AC: 8663 AN: 41462

American (AMR) AF: 0.583 AC: 8895 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2203 AN: 3468

East Asian (EAS) AF: 0.449 AC: 2315 AN: 5154

South Asian (SAS) AF: 0.689 AC: 3319 AN: 4818

European-Finnish (FIN) AF: 0.580 AC: 6117 AN: 10542

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.704 AC: 47865 AN: 67952

Other (OTH) AF: 0.567 AC: 1196 AN: 2110

Alfa AF: 0.660 Hom.: 58684

Bravo AF: 0.513

Asia WGS AF: 0.487 AC: 1694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.36
PhyloP100		-0.075
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: rs1032412; hg19: chr2-163639107;