rs237485

Variant names:

• chr20-49387701-A-G
• rs237485
• NM_004975.4:c.568-12709T>C

Variant summary

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

The ENST00000371741.6(KCNB1):​c.568-12709T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,046 control chromosomes in the GnomAD database, including 9,175 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 0.33 (9175 hom., cov: 31)
• Consequence: KCNB1 ENST00000371741.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 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.568-12709T>C		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.568-12709T>C		intron	N/A	ENSP00000360806.3
	KCNB1	ENST00000635465.1	TSL:1	c.568-12709T>C		intron	N/A	ENSP00000489193.1
	KCNB1	ENST00000635878.1	TSL:5	c.97-88318T>C		intron	N/A	ENSP00000489908.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50740 AN: 151926 Hom.: 9155 Cov.: 31

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.0275

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.334 AC: 50778 AN: 152046 Hom.: 9175 Cov.: 31 AF XY: 0.328 AC XY: 24414 AN XY: 74340

African (AFR) AF: 0.465 AC: 19268 AN: 41434

American (AMR) AF: 0.239 AC: 3657 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1465 AN: 3468

East Asian (EAS) AF: 0.0272 AC: 141 AN: 5186

South Asian (SAS) AF: 0.350 AC: 1681 AN: 4804

European-Finnish (FIN) AF: 0.223 AC: 2367 AN: 10592

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.312 AC: 21184 AN: 67970

Other (OTH) AF: 0.322 AC: 677 AN: 2104

Alfa AF: 0.321 Hom.: 19379

Bravo AF: 0.336

Asia WGS AF: 0.197 AC: 687 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.016
DANN	Benign	0.23
PhyloP100		-2.4
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: rs237485; hg19: chr20-48004238;