rs1051295

Variant names:

• chr20-49372368-A-G
• rs1051295
• NM_004975.4:c.*615T>C

Your query was ambiguous. Multiple possible variants found:

• chr20-49372368-A-G
• chr20-49372368-A-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.*615T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,314 control chromosomes in the GnomAD database, including 4,680 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 0.22 (4675 hom., cov: 32)
  • Exomes 𝑓: 0.21 (5 hom.)
• Consequence: KCNB1 NM_004975.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475
• Publications: 17 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNB1	NM_004975.4	c.*615T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000371741.6	NP_004966.1
KCNB1	XM_011528799.3	c.*615T>C		3_prime_UTR_variant	Exon 3 of 3		XP_011527101.1
LOC105372649	XR_001754659.2	n.1201+40344A>G		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNB1	ENST00000371741.6	c.*615T>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_004975.4	ENSP00000360806.3

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33775 AN: 152044 Hom.: 4657 Cov.: 32

Gnomad AFR AF: 0.0656

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.211 AC: 32 AN: 152 Hom.: 5 Cov.: 0 AF XY: 0.228 AC XY: 21 AN XY: 92

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.293 AC: 17 AN: 58

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.174 AC: 15 AN: 86

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.222 AC: 33821 AN: 152162 Hom.: 4675 Cov.: 32 AF XY: 0.229 AC XY: 17030 AN XY: 74372

African (AFR) AF: 0.0659 AC: 2737 AN: 41548

American (AMR) AF: 0.325 AC: 4967 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 493 AN: 3470

East Asian (EAS) AF: 0.404 AC: 2087 AN: 5164

South Asian (SAS) AF: 0.250 AC: 1204 AN: 4820

European-Finnish (FIN) AF: 0.345 AC: 3648 AN: 10574

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.262 AC: 17846 AN: 67996

Other (OTH) AF: 0.219 AC: 463 AN: 2110

Alfa AF: 0.247 Hom.: 10300

Bravo AF: 0.217

Asia WGS AF: 0.323 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.6
DANN	Benign	0.58
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1051295; hg19: chr20-47988905;