rs496503

Positions:

• chr9-135705128-G-A

Variant summary

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

The NM_020822.3(KCNT1):​c.110+2760G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 152,252 control chromosomes in the GnomAD database, including 57,815 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 0.87 (57815 hom., cov: 33)
• Consequence: KCNT1 NM_020822.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41

Genes affected

KCNT1 (HGNC:18865): (potassium sodium-activated channel subfamily T member 1) Potassium 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 sodium-activated potassium channel subunit which is thought to function in ion conductance and developmental signaling pathways. Mutations in this gene cause the early-onset epileptic disorders, malignant migrating partial seizures of infancy and autosomal dominant nocturnal frontal lobe epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

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 = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNT1	NM_020822.3	c.110+2760G>A		intron_variant		ENST00000371757.7
KCNT1	NM_001272003.2	c.110+2760G>A		intron_variant
KCNT1	XM_011518878.4	c.245+168G>A		intron_variant
KCNT1	XM_011518879.4	c.245+168G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNT1	ENST00000371757.7	c.110+2760G>A		intron_variant		1	NM_020822.3	A2

Frequencies

GnomAD3 genomes AF: 0.868 AC: 132044 AN: 152132 Hom.: 57805 Cov.: 33

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.978

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.830

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.861

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

GnomAD4 genome AF: 0.868 AC: 132101 AN: 152252 Hom.: 57815 Cov.: 33 AF XY: 0.870 AC XY: 64790 AN XY: 74462

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.864

Gnomad4 ASJ AF: 0.847

Gnomad4 EAS AF: 0.836

Gnomad4 SAS AF: 0.911

Gnomad4 FIN AF: 0.966

Gnomad4 NFE AF: 0.926

Gnomad4 OTH AF: 0.861

Alfa AF: 0.912 Hom.: 82715

Bravo AF: 0.852

Asia WGS AF: 0.865 AC: 3010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.39
DANN	Benign	0.45

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: rs496503; hg19: chr9-138596974;