NM_004975.4:c.568-5962A>T

Variant names:

• chr20-49380954-T-A
• rs926672
• NM_004975.4:c.568-5962A>T

Variant summary

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

The NM_004975.4(KCNB1):​c.568-5962A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,984 control chromosomes in the GnomAD database, including 16,482 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 0.46 (16482 hom., cov: 31)
• Consequence: KCNB1 NM_004975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004975.4. 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.568-5962A>T		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.568-5962A>T		intron	N/A	ENSP00000360806.3
	KCNB1	ENST00000635465.1	TSL:1	c.568-5962A>T		intron	N/A	ENSP00000489193.1
	KCNB1	ENST00000635878.1	TSL:5	c.97-81571A>T		intron	N/A	ENSP00000489908.1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70089 AN: 151866 Hom.: 16463 Cov.: 31

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.462 AC: 70154 AN: 151984 Hom.: 16482 Cov.: 31 AF XY: 0.467 AC XY: 34703 AN XY: 74310

African (AFR) AF: 0.384 AC: 15894 AN: 41428

American (AMR) AF: 0.527 AC: 8048 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1529 AN: 3464

East Asian (EAS) AF: 0.563 AC: 2916 AN: 5182

South Asian (SAS) AF: 0.465 AC: 2237 AN: 4814

European-Finnish (FIN) AF: 0.520 AC: 5496 AN: 10570

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32424 AN: 67940

Other (OTH) AF: 0.457 AC: 960 AN: 2100

Alfa AF: 0.317 Hom.: 837

Bravo AF: 0.460

Asia WGS AF: 0.513 AC: 1785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0080
DANN	Benign	0.47
PhyloP100		-2.1
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: rs926672; hg19: chr20-47997491;