rs9323431

Variant names:

• chr14-63101770-A-C
• rs9323431
• ENST00000394964.3:n.238+30T>G

Your query was ambiguous. Multiple possible variants found:

• chr14-63101770-A-C
• chr14-63101770-A-G
• chr14-63101770-A-T

Variant summary

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

The ENST00000394964.3(KCNH5):​n.238+30T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,036 control chromosomes in the GnomAD database, including 1,755 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 0.13 (1755 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: KCNH5 ENST00000394964.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719
• Publications: 4 publications found

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]

KCNH5 Gene-Disease associations (from GenCC):

• infantile-onset epilepsy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy 112

  Inheritance: AD Classification: STRONG Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH5	ENST00000394964.3	n.238+30T>G		intron_variant	Intron 1 of 6	1
KCNH5	ENST00000394968.2	c.-102+30T>G		intron_variant	Intron 1 of 10	2		ENSP00000378419.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20269 AN: 151918 Hom.: 1754 Cov.: 31

Gnomad AFR AF: 0.0620

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.157

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.133 AC: 20280 AN: 152036 Hom.: 1755 Cov.: 31 AF XY: 0.135 AC XY: 10018 AN XY: 74304

African (AFR) AF: 0.0621 AC: 2578 AN: 41484

American (AMR) AF: 0.141 AC: 2146 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 493 AN: 3470

East Asian (EAS) AF: 0.409 AC: 2111 AN: 5156

South Asian (SAS) AF: 0.109 AC: 525 AN: 4828

European-Finnish (FIN) AF: 0.142 AC: 1496 AN: 10548

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10402 AN: 67962

Other (OTH) AF: 0.155 AC: 328 AN: 2110

Alfa AF: 0.145 Hom.: 3284

Bravo AF: 0.135

Asia WGS AF: 0.235 AC: 815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.83
DANN	Benign	0.72
PhyloP100		-0.72
PromoterAI		-0.010	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9323431; hg19: chr14-63568488;