rs1348231

Variant names:

• chr3-19444962-C-T
• rs1348231
• NM_144633.3:c.1376-5144C>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.1376-5144C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 151,962 control chromosomes in the GnomAD database, including 333 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 0.044 (333 hom., cov: 32)
• Consequence: KCNH8 NM_144633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115
• Publications: 1 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH8	NM_144633.3	c.1376-5144C>T		intron_variant	Intron 8 of 15	ENST00000328405.7	NP_653234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH8	ENST00000328405.7	c.1376-5144C>T		intron_variant	Intron 8 of 15	1	NM_144633.3	ENSP00000328813.2
KCNH8	ENST00000452398.5	n.*871-5144C>T		intron_variant	Intron 9 of 15	1		ENSP00000412141.1
ENSG00000287069	ENST00000668274.1	n.352+39389G>A		intron_variant	Intron 1 of 2
ENSG00000287069	ENST00000670571.1	n.654+25393G>A		intron_variant	Intron 4 of 5

Frequencies

GnomAD3 genomes AF: 0.0442 AC: 6705 AN: 151844 Hom.: 329 Cov.: 32

Gnomad AFR AF: 0.0822

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0544

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.0326

Gnomad FIN AF: 0.0147

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.0388

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

GnomAD4 genome AF: 0.0442 AC: 6724 AN: 151962 Hom.: 333 Cov.: 32 AF XY: 0.0446 AC XY: 3316 AN XY: 74282

African (AFR) AF: 0.0823 AC: 3415 AN: 41504

American (AMR) AF: 0.0547 AC: 833 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3462

East Asian (EAS) AF: 0.215 AC: 1108 AN: 5162

South Asian (SAS) AF: 0.0328 AC: 158 AN: 4814

European-Finnish (FIN) AF: 0.0147 AC: 156 AN: 10606

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0130 AC: 881 AN: 67864

Other (OTH) AF: 0.0408 AC: 86 AN: 2108

Alfa AF: 0.0215 Hom.: 80

Bravo AF: 0.0505

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.4
DANN	Benign	0.82
PhyloP100		0.12
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: rs1348231; hg19: chr3-19486454;