rs10510486

Positions:

• chr3-19166287-G-A

Variant summary

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

The NM_144633.3(KCNH8):​c.76+17492G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0291 in 152,166 control chromosomes in the GnomAD database, including 198 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 0.029 (198 hom., cov: 32)
• Consequence: KCNH8 NM_144633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH8	NM_144633.3	c.76+17492G>A		intron_variant		ENST00000328405.7	NP_653234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNH8	ENST00000328405.7	c.76+17492G>A		intron_variant		1	NM_144633.3	ENSP00000328813	P1
KCNH8	ENST00000452398.5	c.76+17492G>A		intron_variant, NMD_transcript_variant		1		ENSP00000412141

Frequencies

GnomAD3 genomes AF: 0.0291 AC: 4425 AN: 152048 Hom.: 197 Cov.: 32

Gnomad AFR AF: 0.0992

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000867

Gnomad OTH AF: 0.0211

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

GnomAD4 genome AF: 0.0291 AC: 4434 AN: 152166 Hom.: 198 Cov.: 32 AF XY: 0.0277 AC XY: 2064 AN XY: 74402

Gnomad4 AFR AF: 0.0992

Gnomad4 AMR AF: 0.00916

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.000472

Gnomad4 NFE AF: 0.000867

Gnomad4 OTH AF: 0.0209

Alfa AF: 0.00679 Hom.: 49

Bravo AF: 0.0335

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.40
DANN	Benign	0.56

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: rs10510486; hg19: chr3-19207779;