rs1348231

chr3-19444962-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
KCNH8	NM_144633.3	c.1376-5144C>T		intron_variant		ENST00000328405.7
LOC105376982	XR_940640.3	n.2616+39389G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNH8	ENST00000328405.7	c.1376-5144C>T		intron_variant		1	NM_144633.3	P1
KCNH8	ENST00000452398.5	c.*871-5144C>T		intron_variant, NMD_transcript_variant		1
	ENST00000670571.1	n.654+25393G>A		intron_variant, non_coding_transcript_variant
	ENST00000668274.1	n.352+39389G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0823

Gnomad4 AMR AF: 0.0547

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.0328

Gnomad4 FIN AF: 0.0147

Gnomad4 NFE AF: 0.0130

Gnomad4 OTH AF: 0.0408

Alfa AF: 0.0207 Hom.: 64

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

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: rs1348231; hg19: chr3-19486454;