rs572845

Variant names:

• chr20-49460077-G-A
• rs572845
• NM_004975.4:c.567+21837C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-49460077-G-A
• chr20-49460077-G-C
• chr20-49460077-G-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.567+21837C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,056 control chromosomes in the GnomAD database, including 7,417 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 0.31 (7417 hom., cov: 32)
• Consequence: KCNB1 NM_004975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 9 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

ENSG00000302258 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNB1	NM_004975.4	c.567+21837C>T		intron_variant	Intron 1 of 1	ENST00000371741.6	NP_004966.1
KCNB1	XM_011528799.3	c.567+21837C>T		intron_variant	Intron 2 of 2		XP_011527101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNB1	ENST00000371741.6	c.567+21837C>T		intron_variant	Intron 1 of 1	1	NM_004975.4	ENSP00000360806.3

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46424 AN: 151938 Hom.: 7418 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.305 AC: 46425 AN: 152056 Hom.: 7417 Cov.: 32 AF XY: 0.304 AC XY: 22567 AN XY: 74310

African (AFR) AF: 0.246 AC: 10195 AN: 41478

American (AMR) AF: 0.297 AC: 4530 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1576 AN: 3466

East Asian (EAS) AF: 0.113 AC: 584 AN: 5186

South Asian (SAS) AF: 0.306 AC: 1473 AN: 4808

European-Finnish (FIN) AF: 0.314 AC: 3325 AN: 10580

Middle Eastern (MID) AF: 0.445 AC: 130 AN: 292

European-Non Finnish (NFE) AF: 0.349 AC: 23701 AN: 67948

Other (OTH) AF: 0.343 AC: 724 AN: 2110

Alfa AF: 0.332 Hom.: 19013

Bravo AF: 0.299

Asia WGS AF: 0.203 AC: 705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.83
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: rs572845; hg19: chr20-48076614;