1-196549893-T-C

Position:

• chr1-196549893-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.96-57552A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 151,740 control chromosomes in the GnomAD database, including 49,485 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 (49485 hom., cov: 31)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139

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 (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNT2	NM_198503.5	c.96-57552A>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.96-57552A>G		intron_variant		1	NM_198503.5	ENSP00000294725	P4

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118052 AN: 151620 Hom.: 49470 Cov.: 31

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: 0.920

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.828

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

GnomAD4 genome AF: 0.778 AC: 118101 AN: 151740 Hom.: 49485 Cov.: 31 AF XY: 0.782 AC XY: 58016 AN XY: 74168

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: 0.911

Gnomad4 OTH AF: 0.829

Alfa AF: 0.902 Hom.: 119688

Bravo AF: 0.767

Asia WGS AF: 0.894 AC: 3109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.25

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: rs10754192; hg19: chr1-196519023;