chr20-49372064-T-C

Variant names:

• chr20-49372064-T-C
• rs3331
• NM_004975.4:c.*919A>G

Variant summary

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

The NM_004975.4(KCNB1):​c.*919A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.048 in 152,692 control chromosomes in the GnomAD database, including 194 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 0.048 (194 hom., cov: 32)
  • Exomes 𝑓: 0.033 (0 hom.)
• Consequence: KCNB1 NM_004975.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0735 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.*919A>G		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.*919A>G		3_prime_UTR	Exon 2 of 2	ENSP00000360806.3
	KCNB1	ENST00000635465.1	TSL:1	c.*919A>G		3_prime_UTR	Exon 3 of 3	ENSP00000489193.1
	KCNB1	ENST00000635878.1	TSL:5	c.97-72681A>G		intron	N/A	ENSP00000489908.1

Frequencies

GnomAD3 genomes AF: 0.0479 AC: 7283 AN: 152174 Hom.: 190 Cov.: 32

Gnomad AFR AF: 0.0620

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0292

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.0797

Gnomad SAS AF: 0.0757

Gnomad FIN AF: 0.0284

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0434

Gnomad OTH AF: 0.0416

GnomAD4 exome AF: 0.0325 AC: 13 AN: 400 Hom.: 0 Cov.: 0 AF XY: 0.0474 AC XY: 11 AN XY: 232

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: 0.0330 AC: 13 AN: 394

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0481 AC: 7318 AN: 152292 Hom.: 194 Cov.: 32 AF XY: 0.0477 AC XY: 3549 AN XY: 74468

African (AFR) AF: 0.0627 AC: 2607 AN: 41574

American (AMR) AF: 0.0292 AC: 446 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0208 AC: 72 AN: 3468

East Asian (EAS) AF: 0.0799 AC: 414 AN: 5184

South Asian (SAS) AF: 0.0749 AC: 362 AN: 4830

European-Finnish (FIN) AF: 0.0284 AC: 301 AN: 10614

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0434 AC: 2954 AN: 68004

Other (OTH) AF: 0.0412 AC: 87 AN: 2114

Alfa AF: 0.0451 Hom.: 49

Bravo AF: 0.0478

Asia WGS AF: 0.0790 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.67
PhyloP100		-1.6
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: rs3331; hg19: chr20-47988601;