1-196607234-C-G

Position:

• chr1-196607234-C-G

Variant summary

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

The ENST00000294725.14(KCNT2):​c.95+981G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,148 control chromosomes in the GnomAD database, including 49,461 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 0.78 (49461 hom., cov: 33)
• Consequence: KCNT2 ENST00000294725.14 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119

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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNT2	NM_198503.5	c.95+981G>C		intron_variant		ENST00000294725.14	NP_940905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNT2	ENST00000294725.14	c.95+981G>C		intron_variant		1	NM_198503.5	ENSP00000294725	P4

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118206 AN: 152030 Hom.: 49450 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.974

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.921

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.825

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

GnomAD4 genome AF: 0.777 AC: 118253 AN: 152148 Hom.: 49461 Cov.: 33 AF XY: 0.781 AC XY: 58126 AN XY: 74394

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.894

Gnomad4 ASJ AF: 0.974

Gnomad4 EAS AF: 0.966

Gnomad4 SAS AF: 0.921

Gnomad4 FIN AF: 0.859

Gnomad4 NFE AF: 0.908

Gnomad4 OTH AF: 0.825

Alfa AF: 0.760 Hom.: 2671

Bravo AF: 0.766

Asia WGS AF: 0.892 AC: 3101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.74

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: rs1360143; hg19: chr1-196576364;