7-150970122-C-T

Position:

• chr7-150970122-C-T

Variant summary

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

The NM_000238.4(KCNH2):​c.307+4589G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,972 control chromosomes in the GnomAD database, including 20,473 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 0.49 (20473 hom., cov: 31)
• Consequence: KCNH2 NM_000238.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530

Genes affected

KCNH2 (HGNC:6251): (potassium voltage-gated channel subfamily H member 2) This gene encodes a component of a voltage-activated potassium channel found in cardiac muscle, nerve cells, and microglia. Four copies of this protein interact with one copy of the KCNE2 protein to form a functional potassium channel. Mutations in this gene can cause long QT syndrome type 2 (LQT2). Transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, May 2022]

KCNH2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH2	NM_000238.4	c.307+4589G>A		intron_variant		ENST00000262186.10	NP_000229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNH2	ENST00000262186.10	c.307+4589G>A		intron_variant		1	NM_000238.4	ENSP00000262186.5
KCNH2	ENST00000532957.5	n.530+4589G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74983 AN: 151854 Hom.: 20424 Cov.: 31

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.494 AC: 75093 AN: 151972 Hom.: 20473 Cov.: 31 AF XY: 0.499 AC XY: 37096 AN XY: 74292

Gnomad4 AFR AF: 0.706

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.778

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.465

Alfa AF: 0.391 Hom.: 27955

Bravo AF: 0.514

Asia WGS AF: 0.590 AC: 2049 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.6
DANN	Benign	0.71

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: rs3807375; hg19: chr7-150667210;