rs237477

Variant names:

• chr20-49440911-C-T
• rs237477
• NM_004975.4:c.567+41003G>A

Variant summary

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

The ENST00000371741.6(KCNB1):​c.567+41003G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 152,196 control chromosomes in the GnomAD database, including 40,419 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 0.72 (40395 hom., cov: 32)
  • Exomes 𝑓: 0.71 (24 hom.)
• Consequence: KCNB1 ENST00000371741.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 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.567+41003G>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.567+41003G>A		intron	N/A	ENSP00000360806.3
	KCNB1	ENST00000635465.1	TSL:1	c.567+41003G>A		intron	N/A	ENSP00000489193.1
	ENSG00000290421	ENST00000637341.1	TSL:5	n.945C>T		non_coding_transcript_exon	Exon 8 of 8

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108658 AN: 151982 Hom.: 40342 Cov.: 32

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.726

GnomAD4 exome AF: 0.713 AC: 67 AN: 94 Hom.: 24 Cov.: 0 AF XY: 0.722 AC XY: 52 AN XY: 72

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 3 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.718 AC: 56 AN: 78

Other (OTH) AF: 0.500 AC: 3 AN: 6

GnomAD4 genome AF: 0.715 AC: 108764 AN: 152102 Hom.: 40395 Cov.: 32 AF XY: 0.714 AC XY: 53081 AN XY: 74334

African (AFR) AF: 0.930 AC: 38615 AN: 41528

American (AMR) AF: 0.708 AC: 10832 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2497 AN: 3468

East Asian (EAS) AF: 0.709 AC: 3668 AN: 5176

South Asian (SAS) AF: 0.718 AC: 3454 AN: 4812

European-Finnish (FIN) AF: 0.556 AC: 5865 AN: 10550

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41618 AN: 67952

Other (OTH) AF: 0.719 AC: 1521 AN: 2114

Alfa AF: 0.651 Hom.: 64093

Bravo AF: 0.734

Asia WGS AF: 0.709 AC: 2466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.41
PhyloP100		-0.15
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: rs237477; hg19: chr20-48057448;