chr1-196342383-G-A

Position:

• chr1-196342383-G-A

Variant summary

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

The NM_198503.5(KCNT2):​c.1404-155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 378,002 control chromosomes in the GnomAD database, including 46,705 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 0.42 (14734 hom., cov: 26)
  • Exomes 𝑓: 0.51 (31971 hom.)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNT2	NM_198503.5	c.1404-155C>T		intron_variant		ENST00000294725.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNT2	ENST00000294725.14	c.1404-155C>T		intron_variant		1	NM_198503.5	P4

Frequencies

GnomAD3 genomes AF: 0.416 AC: 60513 AN: 145420 Hom.: 14748 Cov.: 26

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.453

GnomAD4 exome AF: 0.514 AC: 119614 AN: 232522 Hom.: 31971 AF XY: 0.516 AC XY: 61944 AN XY: 120138

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.442

Gnomad4 ASJ exome AF: 0.580

Gnomad4 EAS exome AF: 0.715

Gnomad4 SAS exome AF: 0.574

Gnomad4 FIN exome AF: 0.465

Gnomad4 NFE exome AF: 0.508

Gnomad4 OTH exome AF: 0.501

GnomAD4 genome AF: 0.416 AC: 60479 AN: 145480 Hom.: 14734 Cov.: 26 AF XY: 0.419 AC XY: 29710 AN XY: 70832

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.512

Gnomad4 OTH AF: 0.452

Alfa AF: 0.420 Hom.: 2018

Bravo AF: 0.396

Asia WGS AF: 0.574 AC: 1993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.32

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: rs6658788; hg19: chr1-196311513;