chr1-196377423-A-G

Position:

• chr1-196377423-A-G

Variant summary

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

The NM_198503.5(KCNT2):​c.1295-4175T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 151,956 control chromosomes in the GnomAD database, including 1,225 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 0.11 (1225 hom., cov: 31)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNT2	NM_198503.5	c.1295-4175T>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.1295-4175T>C		intron_variant		1	NM_198503.5	ENSP00000294725	P4

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16042 AN: 151838 Hom.: 1225 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0692

Gnomad ASJ AF: 0.0427

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.0457

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0734

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.106 AC: 16054 AN: 151956 Hom.: 1225 Cov.: 31 AF XY: 0.101 AC XY: 7472 AN XY: 74280

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.0691

Gnomad4 ASJ AF: 0.0427

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0350

Gnomad4 FIN AF: 0.0457

Gnomad4 NFE AF: 0.0734

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0859 Hom.: 474

Bravo AF: 0.112

Asia WGS AF: 0.0280 AC: 98 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.1
DANN	Benign	0.80

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: rs10494742; hg19: chr1-196346553;