chr3-19183006-G-A

Variant names:

• chr3-19183006-G-A
• rs997384
• NM_144633.3:c.76+34211G>A

Variant summary

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

The NM_144633.3(KCNH8):​c.76+34211G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 152,198 control chromosomes in the GnomAD database, including 53,052 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 0.83 (53052 hom., cov: 33)
• Consequence: KCNH8 NM_144633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH8	NM_144633.3	c.76+34211G>A		intron_variant	Intron 1 of 15	ENST00000328405.7	NP_653234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH8	ENST00000328405.7	c.76+34211G>A		intron_variant	Intron 1 of 15	1	NM_144633.3	ENSP00000328813.2
KCNH8	ENST00000452398.5	n.76+34211G>A		intron_variant	Intron 1 of 15	1		ENSP00000412141.1

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126469 AN: 152080 Hom.: 52986 Cov.: 33

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.832 AC: 126596 AN: 152198 Hom.: 53052 Cov.: 33 AF XY: 0.832 AC XY: 61912 AN XY: 74394

African (AFR) AF: 0.924 AC: 38404 AN: 41558

American (AMR) AF: 0.830 AC: 12680 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2671 AN: 3470

East Asian (EAS) AF: 0.642 AC: 3307 AN: 5152

South Asian (SAS) AF: 0.773 AC: 3730 AN: 4828

European-Finnish (FIN) AF: 0.862 AC: 9130 AN: 10596

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54233 AN: 67990

Other (OTH) AF: 0.807 AC: 1705 AN: 2114

Alfa AF: 0.803 Hom.: 163496

Bravo AF: 0.830

Asia WGS AF: 0.705 AC: 2442 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
DANN	Benign	0.55
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: rs997384; hg19: chr3-19224498;