rs6573463

Positions:

• chr14-62885331-A-C
• chr14-62885331-A-G

Variant summary

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

The ENST00000322893.12(KCNH5):​c.1370-35479T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,050 control chromosomes in the GnomAD database, including 41,143 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 0.73 (41143 hom., cov: 33)
• Consequence: KCNH5 ENST00000322893.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.571

Genes affected

KCNH5 (HGNC:6254): (potassium voltage-gated channel subfamily H member 5) This gene encodes a member of voltage-gated potassium channels. Members of this family have diverse functions, including regulating neurotransmitter and hormone release, cardiac function, and cell volume. This protein is an outward-rectifying, noninactivating channel. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH5	NM_139318.5	c.1370-35479T>G		intron_variant		ENST00000322893.12	NP_647479.2
KCNH5	NM_172375.3	c.1370-35479T>G		intron_variant			NP_758963.1
KCNH5	XM_047431275.1	c.1370-35479T>G		intron_variant			XP_047287231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNH5	ENST00000322893.12	c.1370-35479T>G		intron_variant		1	NM_139318.5	ENSP00000321427	P1
KCNH5	ENST00000420622.6	c.1370-35479T>G		intron_variant		1		ENSP00000395439
KCNH5	ENST00000394968.2	c.1196-35479T>G		intron_variant		2		ENSP00000378419

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110307 AN: 151934 Hom.: 41098 Cov.: 33

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.726 AC: 110408 AN: 152050 Hom.: 41143 Cov.: 33 AF XY: 0.729 AC XY: 54174 AN XY: 74304

Gnomad4 AFR AF: 0.865

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.736

Alfa AF: 0.662 Hom.: 29821

Bravo AF: 0.732

Asia WGS AF: 0.892 AC: 3091 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.59
DANN	Benign	0.69

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: rs6573463; hg19: chr14-63352049;