rs36103415

Positions:

• chr14-63006481-GA-G
• chr14-63006481-GA-GAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_139318.5(KCNH5):​c.198-10del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 1,465,854 control chromosomes in the GnomAD database, including 1,568 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.048 (203 hom., cov: 32)
  • Exomes 𝑓: 0.043 (1365 hom.)
• Consequence: KCNH5 NM_139318.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.114

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 -10 ACMG points.

• BP6: Variant 14-63006481-GA-G is Benign according to our data. Variant chr14-63006481-GA-G is described in ClinVar as [Benign]. Clinvar id is 241862.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH5	NM_139318.5	c.198-10del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000322893.12	NP_647479.2
KCNH5	NM_172375.3	c.198-10del		splice_polypyrimidine_tract_variant, intron_variant			NP_758963.1
KCNH5	XM_047431275.1	c.198-10del		splice_polypyrimidine_tract_variant, intron_variant			XP_047287231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNH5	ENST00000322893.12	c.198-10del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_139318.5	ENSP00000321427	P1
KCNH5	ENST00000420622.6	c.198-10del		splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000395439
KCNH5	ENST00000394964.3	n.363-10del		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1
KCNH5	ENST00000394968.2	c.24-10del		splice_polypyrimidine_tract_variant, intron_variant		2		ENSP00000378419

Frequencies

GnomAD3 genomes AF: 0.0479 AC: 7256 AN: 151510 Hom.: 202 Cov.: 32

Gnomad AFR AF: 0.0485

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0356

Gnomad ASJ AF: 0.0188

Gnomad EAS AF: 0.0630

Gnomad SAS AF: 0.0217

Gnomad FIN AF: 0.0917

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0454

Gnomad OTH AF: 0.0376

GnomAD3 exomes AF: 0.0468 AC: 10735 AN: 229392 Hom.: 293 AF XY: 0.0450 AC XY: 5594 AN XY: 124210

Gnomad AFR exome AF: 0.0506

Gnomad AMR exome AF: 0.0309

Gnomad ASJ exome AF: 0.0244

Gnomad EAS exome AF: 0.0700

Gnomad SAS exome AF: 0.0187

Gnomad FIN exome AF: 0.0887

Gnomad NFE exome AF: 0.0484

Gnomad OTH exome AF: 0.0430

GnomAD4 exome AF: 0.0427 AC: 56092 AN: 1314228 Hom.: 1365 Cov.: 18 AF XY: 0.0421 AC XY: 27752 AN XY: 659622

Gnomad4 AFR exome AF: 0.0495

Gnomad4 AMR exome AF: 0.0298

Gnomad4 ASJ exome AF: 0.0212

Gnomad4 EAS exome AF: 0.0528

Gnomad4 SAS exome AF: 0.0170

Gnomad4 FIN exome AF: 0.0830

Gnomad4 NFE exome AF: 0.0435

Gnomad4 OTH exome AF: 0.0390

GnomAD4 genome AF: 0.0479 AC: 7258 AN: 151626 Hom.: 203 Cov.: 32 AF XY: 0.0494 AC XY: 3658 AN XY: 74040

Gnomad4 AFR AF: 0.0485

Gnomad4 AMR AF: 0.0356

Gnomad4 ASJ AF: 0.0188

Gnomad4 EAS AF: 0.0627

Gnomad4 SAS AF: 0.0217

Gnomad4 FIN AF: 0.0917

Gnomad4 NFE AF: 0.0454

Gnomad4 OTH AF: 0.0367

Alfa AF: 0.0232 Hom.: 14

Bravo AF: 0.0445

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

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: rs36103415; hg19: chr14-63473199;