NM_144633.3:c.1178-3211C>T

Variant names:

• chr3-19434953-C-T
• rs10514672
• NM_144633.3:c.1178-3211C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144633.3(KCNH8):​c.1178-3211C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0341 in 151,930 control chromosomes in the GnomAD database, including 223 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 0.034 (223 hom., cov: 32)
• Consequence: KCNH8 NM_144633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 2 publications found

Genes affected

KCNH8 (HGNC:18864): (potassium voltage-gated channel subfamily H member 8) 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. [provided by RefSeq, Jul 2008]

ENSG00000287069 (HGNC:):

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 = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH8	NM_144633.3	c.1178-3211C>T		intron_variant	Intron 7 of 15	ENST00000328405.7	NP_653234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH8	ENST00000328405.7	c.1178-3211C>T		intron_variant	Intron 7 of 15	1	NM_144633.3	ENSP00000328813.2
KCNH8	ENST00000452398.5	n.*673-3211C>T		intron_variant	Intron 8 of 15	1		ENSP00000412141.1
ENSG00000287069	ENST00000668274.1	n.353-34306G>A		intron_variant	Intron 1 of 2
ENSG00000287069	ENST00000670571.1	n.655-34306G>A		intron_variant	Intron 4 of 5

Frequencies

GnomAD3 genomes AF: 0.0340 AC: 5165 AN: 151812 Hom.: 217 Cov.: 32

Gnomad AFR AF: 0.0480

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0478

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.0328

Gnomad FIN AF: 0.0159

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.0331

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

GnomAD4 genome AF: 0.0341 AC: 5185 AN: 151930 Hom.: 223 Cov.: 32 AF XY: 0.0350 AC XY: 2596 AN XY: 74250

African (AFR) AF: 0.0481 AC: 1992 AN: 41404

American (AMR) AF: 0.0482 AC: 734 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 73 AN: 3472

East Asian (EAS) AF: 0.206 AC: 1064 AN: 5164

South Asian (SAS) AF: 0.0330 AC: 159 AN: 4818

European-Finnish (FIN) AF: 0.0159 AC: 168 AN: 10554

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0134 AC: 908 AN: 67968

Other (OTH) AF: 0.0351 AC: 74 AN: 2108

Alfa AF: 0.0220 Hom.: 264

Bravo AF: 0.0377

Asia WGS AF: 0.108 AC: 373 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.33
DANN	Benign	0.76
PhyloP100		-1.1
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: rs10514672; hg19: chr3-19476445;