1-196416519-T-C

Position:

• chr1-196416519-T-C

Variant summary

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

The ENST00000294725.14(KCNT2):​c.1185+6531A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 151,806 control chromosomes in the GnomAD database, including 37,066 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 0.70 (37066 hom., cov: 30)
• Consequence: KCNT2 ENST00000294725.14 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNT2	NM_198503.5	c.1185+6531A>G		intron_variant		ENST00000294725.14	NP_940905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNT2	ENST00000294725.14	c.1185+6531A>G		intron_variant		1	NM_198503.5	ENSP00000294725	P4

Frequencies

GnomAD3 genomes AF: 0.698 AC: 105868 AN: 151688 Hom.: 37027 Cov.: 30

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.698 AC: 105962 AN: 151806 Hom.: 37066 Cov.: 30 AF XY: 0.693 AC XY: 51380 AN XY: 74138

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.663

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.709

Alfa AF: 0.699 Hom.: 38477

Bravo AF: 0.702

Asia WGS AF: 0.675 AC: 2348 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.7
DANN	Benign	0.75

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: rs3927686; hg19: chr1-196385649; COSMIC: COSV54070780;