20-49407795-C-T

Variant names:

• chr20-49407795-C-T
• rs237451
• NM_004975.4:c.568-32803G>A

Variant summary

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

The ENST00000371741.6(KCNB1):​c.568-32803G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,002 control chromosomes in the GnomAD database, including 9,369 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 0.35 (9369 hom., cov: 31)
• Consequence: KCNB1 ENST00000371741.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 1 publications found

Genes affected

KCNB1 (HGNC:6231): (potassium voltage-gated channel subfamily B member 1) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shab-related subfamily. This member is a delayed rectifier potassium channel and its activity is modulated by some other family members. [provided by RefSeq, Jul 2008]

KCNB1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 26

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000290421 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371741.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB1	NM_004975.4	MANE Select	c.568-32803G>A		intron	N/A	NP_004966.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB1	ENST00000371741.6	TSL:1 MANE Select	c.568-32803G>A		intron	N/A	ENSP00000360806.3
	KCNB1	ENST00000635465.1	TSL:1	c.568-32803G>A		intron	N/A	ENSP00000489193.1
	KCNB1	ENST00000635878.1	TSL:5	c.96+74119G>A		intron	N/A	ENSP00000489908.1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53038 AN: 151884 Hom.: 9373 Cov.: 31

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.349 AC: 53035 AN: 152002 Hom.: 9369 Cov.: 31 AF XY: 0.349 AC XY: 25957 AN XY: 74294

African (AFR) AF: 0.329 AC: 13656 AN: 41488

American (AMR) AF: 0.393 AC: 6007 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1585 AN: 3472

East Asian (EAS) AF: 0.372 AC: 1912 AN: 5146

South Asian (SAS) AF: 0.306 AC: 1468 AN: 4800

European-Finnish (FIN) AF: 0.344 AC: 3632 AN: 10560

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23652 AN: 67940

Other (OTH) AF: 0.381 AC: 804 AN: 2110

Alfa AF: 0.355 Hom.: 2187

Bravo AF: 0.354

Asia WGS AF: 0.361 AC: 1252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.72
DANN	Benign	0.46
PhyloP100		-2.0
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

Other links and lift over

dbSNP: rs237451; hg19: chr20-48024332; COSMIC: COSV65566876;