rs237450

Variant names:

• chr20-49365591-G-A
• rs237450
• NM_004975.4:c.*7392C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-49365591-G-A
• chr20-49365591-G-C
• chr20-49365591-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.*7392C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,146 control chromosomes in the GnomAD database, including 2,259 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 0.16 (2259 hom., cov: 32)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: KCNB1 NM_004975.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.865
• Publications: 6 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 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.*7392C>T		3_prime_UTR	Exon 2 of 2	NP_004966.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB1	ENST00000371741.6	TSL:1 MANE Select	c.*7392C>T		3_prime_UTR	Exon 2 of 2	ENSP00000360806.3
	KCNB1	ENST00000635878.1	TSL:5	c.97-66208C>T		intron	N/A	ENSP00000489908.1
	KCNB1	ENST00000636838.1	TSL:5	n.610+6750C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24718 AN: 152016 Hom.: 2260 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.0833 AC: 1 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 1 AN XY: 12

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.162 AC: 24709 AN: 152134 Hom.: 2259 Cov.: 32 AF XY: 0.161 AC XY: 12010 AN XY: 74380

African (AFR) AF: 0.259 AC: 10751 AN: 41460

American (AMR) AF: 0.140 AC: 2143 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 484 AN: 3470

East Asian (EAS) AF: 0.128 AC: 662 AN: 5176

South Asian (SAS) AF: 0.114 AC: 552 AN: 4824

European-Finnish (FIN) AF: 0.102 AC: 1077 AN: 10604

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.127 AC: 8609 AN: 68004

Other (OTH) AF: 0.134 AC: 284 AN: 2114

Alfa AF: 0.143 Hom.: 3502

Bravo AF: 0.168

Asia WGS AF: 0.112 AC: 390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.55
PhyloP100		0.86
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: rs237450; hg19: chr20-47982128;