1-196456003-A-G

Variant names:

• chr1-196456003-A-G
• rs10494743
• NM_198503.5:c.638+9290T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198503.5(KCNT2):​c.638+9290T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,928 control chromosomes in the GnomAD database, including 19,533 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 0.47 (19533 hom., cov: 32)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNT2	NM_198503.5	c.638+9290T>C		intron_variant	Intron 8 of 27	ENST00000294725.14	NP_940905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNT2	ENST00000294725.14	c.638+9290T>C		intron_variant	Intron 8 of 27	1	NM_198503.5	ENSP00000294725.8

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71922 AN: 151808 Hom.: 19530 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.473 AC: 71936 AN: 151928 Hom.: 19533 Cov.: 32 AF XY: 0.472 AC XY: 35055 AN XY: 74238

African (AFR) AF: 0.183 AC: 7583 AN: 41490

American (AMR) AF: 0.511 AC: 7773 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2105 AN: 3466

East Asian (EAS) AF: 0.611 AC: 3127 AN: 5122

South Asian (SAS) AF: 0.606 AC: 2925 AN: 4826

European-Finnish (FIN) AF: 0.515 AC: 5439 AN: 10570

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41099 AN: 67918

Other (OTH) AF: 0.522 AC: 1103 AN: 2114

Alfa AF: 0.574 Hom.: 41508

Bravo AF: 0.463

Asia WGS AF: 0.558 AC: 1942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.92
DANN	Benign	0.54
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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

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Other links and lift over

dbSNP: rs10494743; hg19: chr1-196425133; COSMIC: COSV54070932;