chr3-19401114-T-G

Variant names:

• chr3-19401114-T-G
• rs10514673
• NM_144633.3:c.1177+5803T>G

Variant summary

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

The NM_144633.3(KCNH8):​c.1177+5803T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 152,024 control chromosomes in the GnomAD database, including 298 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 (298 hom., cov: 32)
• Consequence: KCNH8 NM_144633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.630
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144633.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH8	NM_144633.3	MANE Select	c.1177+5803T>G		intron	N/A	NP_653234.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH8	ENST00000328405.7	TSL:1 MANE Select	c.1177+5803T>G		intron	N/A	ENSP00000328813.2	Q96L42-1
	KCNH8	ENST00000452398.5	TSL:1	n.*672+5803T>G		intron	N/A	ENSP00000412141.1	F8WCG6
	KCNH8	ENST00000938024.1		c.812-37050T>G		intron	N/A	ENSP00000608083.1

Frequencies

GnomAD3 genomes AF: 0.0434 AC: 6600 AN: 151904 Hom.: 285 Cov.: 32

Gnomad AFR AF: 0.0771

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0591

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0143

Gnomad OTH AF: 0.0426

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

GnomAD4 genome AF: 0.0437 AC: 6644 AN: 152024 Hom.: 298 Cov.: 32 AF XY: 0.0447 AC XY: 3319 AN XY: 74326

African (AFR) AF: 0.0775 AC: 3215 AN: 41484

American (AMR) AF: 0.0595 AC: 905 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3468

East Asian (EAS) AF: 0.197 AC: 1012 AN: 5146

South Asian (SAS) AF: 0.0290 AC: 140 AN: 4824

European-Finnish (FIN) AF: 0.0185 AC: 197 AN: 10620

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0143 AC: 974 AN: 67948

Other (OTH) AF: 0.0483 AC: 102 AN: 2112

Alfa AF: 0.0275 Hom.: 152

Bravo AF: 0.0493

Asia WGS AF: 0.112 AC: 388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.32
PhyloP100		0.63
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: rs10514673; hg19: chr3-19442606;