14-62726230-T-C

Position:

• chr14-62726230-T-C

Variant summary

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

The NM_139318.5(KCNH5):​c.2020-17775A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.931 in 152,226 control chromosomes in the GnomAD database, including 66,634 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 0.93 (66634 hom., cov: 31)
• Consequence: KCNH5 NM_139318.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH5	NM_139318.5	c.2020-17775A>G		intron_variant		ENST00000322893.12	NP_647479.2
KCNH5	NM_172375.3	c.1823-17775A>G		intron_variant			NP_758963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNH5	ENST00000322893.12	c.2020-17775A>G		intron_variant		1	NM_139318.5	ENSP00000321427	P1
KCNH5	ENST00000420622.6	c.1823-17775A>G		intron_variant		1		ENSP00000395439
KCNH5	ENST00000394968.2	c.1846-13514A>G		intron_variant		2		ENSP00000378419

Frequencies

GnomAD3 genomes AF: 0.931 AC: 141624 AN: 152108 Hom.: 66582 Cov.: 31

Gnomad AFR AF: 0.788

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.964

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.987

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.937

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

GnomAD4 genome AF: 0.931 AC: 141734 AN: 152226 Hom.: 66634 Cov.: 31 AF XY: 0.932 AC XY: 69347 AN XY: 74420

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.964

Gnomad4 ASJ AF: 0.977

Gnomad4 EAS AF: 0.907

Gnomad4 SAS AF: 0.988

Gnomad4 FIN AF: 0.987

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.937

Alfa AF: 0.959 Hom.: 8745

Bravo AF: 0.923

Asia WGS AF: 0.946 AC: 3279 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.074
DANN	Benign	0.20

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: rs2101552; hg19: chr14-63192948;