1-196433643-T-C

Position:

• chr1-196433643-T-C

Variant summary

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

The NM_198503.5(KCNT2):​c.639-3886A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 151,912 control chromosomes in the GnomAD database, including 29,850 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 0.62 (29850 hom., cov: 32)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.869

Genes affected

KCNT2 (HGNC:18866): (potassium sodium-activated channel subfamily T member 2) Enables chloride-activated potassium channel activity. Involved in potassium ion export across plasma membrane. Located in plasma membrane. Implicated in developmental and epileptic encephalopathy 57. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNT2	NM_198503.5	c.639-3886A>G		intron_variant		ENST00000294725.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNT2	ENST00000294725.14	c.639-3886A>G		intron_variant		1	NM_198503.5	P4

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94004 AN: 151792 Hom.: 29832 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.619 AC: 94069 AN: 151912 Hom.: 29850 Cov.: 32 AF XY: 0.618 AC XY: 45861 AN XY: 74216

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.654

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.645

Alfa AF: 0.684 Hom.: 46548

Bravo AF: 0.612

Asia WGS AF: 0.655 AC: 2275 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.90
DANN	Benign	0.47

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: rs2878557; hg19: chr1-196402773; COSMIC: COSV54070883;