2-162669601-A-C

Position:

• chr2-162669601-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033272.4(KCNH7):​c.308-132521T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,154 control chromosomes in the GnomAD database, including 2,258 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 0.16 (2258 hom., cov: 32)
• Consequence: KCNH7 NM_033272.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH7	NM_033272.4	c.308-132521T>G		intron_variant		ENST00000332142.10	NP_150375.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNH7	ENST00000332142.10	c.308-132521T>G		intron_variant		1	NM_033272.4	ENSP00000331727.5
KCNH7	ENST00000328032.8	c.308-132521T>G		intron_variant		1		ENSP00000333781.4

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24160 AN: 152036 Hom.: 2252 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.159 AC: 24179 AN: 152154 Hom.: 2258 Cov.: 32 AF XY: 0.163 AC XY: 12103 AN XY: 74378

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.152

Alfa AF: 0.127 Hom.: 642

Bravo AF: 0.156

Asia WGS AF: 0.324 AC: 1126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.53
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs1435013; hg19: chr2-163526111;