20-49358478-A-G

Variant names:

• chr20-49358478-A-G
• rs237484
• ENST00000635878.1:c.97-59095T>C

Variant summary

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

The ENST00000637575.1(ENSG00000290421):​n.430-12024A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,882 control chromosomes in the GnomAD database, including 26,006 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 0.58 (26006 hom., cov: 30)
• Consequence: ENSG00000290421 ENST00000637575.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.915
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000637575.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB1	ENST00000635878.1	TSL:5	c.97-59095T>C		intron	N/A	ENSP00000489908.1
	KCNB1	ENST00000636838.1	TSL:5	n.610+13863T>C		intron	N/A
	ENSG00000290421	ENST00000637091.1	TSL:5	n.223-12024A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88263 AN: 151764 Hom.: 25951 Cov.: 30

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.582 AC: 88369 AN: 151882 Hom.: 26006 Cov.: 30 AF XY: 0.584 AC XY: 43368 AN XY: 74204

African (AFR) AF: 0.658 AC: 27239 AN: 41380

American (AMR) AF: 0.584 AC: 8910 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1562 AN: 3470

East Asian (EAS) AF: 0.646 AC: 3322 AN: 5146

South Asian (SAS) AF: 0.596 AC: 2868 AN: 4814

European-Finnish (FIN) AF: 0.550 AC: 5803 AN: 10548

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36845 AN: 67940

Other (OTH) AF: 0.539 AC: 1139 AN: 2114

Alfa AF: 0.550 Hom.: 16340

Bravo AF: 0.585

Asia WGS AF: 0.606 AC: 2108 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.70
DANN	Benign	0.48
PhyloP100		-0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs237484; hg19: chr20-47975015;