chr8-72743227-C-T

Variant names:

• chr8-72743227-C-T
• rs1965805
• NM_004770.3:c.579+174914C>T

Variant summary

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

The NM_004770.3(KCNB2):​c.579+174914C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,174 control chromosomes in the GnomAD database, including 41,148 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 (41148 hom., cov: 33)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327
• Publications: 1 publications found

Genes affected

KCNB2 (HGNC:6232): (potassium voltage-gated channel subfamily B member 2) 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. The gene is expressed in gastrointestinal smooth muscle cells. [provided by RefSeq, Jul 2008]

KCNB2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ENSG00000253726 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004770.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB2	NM_004770.3	MANE Select	c.579+174914C>T		intron	N/A	NP_004761.2
	LOC101926908	NR_110656.1		n.58-6111C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB2	ENST00000523207.2	TSL:1 MANE Select	c.579+174914C>T		intron	N/A	ENSP00000430846.1	Q92953
	ENSG00000253726	ENST00000519427.1	TSL:2	n.58-6111C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110040 AN: 152054 Hom.: 41085 Cov.: 33

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.724 AC: 110169 AN: 152174 Hom.: 41148 Cov.: 33 AF XY: 0.715 AC XY: 53197 AN XY: 74366

African (AFR) AF: 0.906 AC: 37629 AN: 41542

American (AMR) AF: 0.617 AC: 9433 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2064 AN: 3470

East Asian (EAS) AF: 0.435 AC: 2250 AN: 5172

South Asian (SAS) AF: 0.575 AC: 2769 AN: 4816

European-Finnish (FIN) AF: 0.632 AC: 6678 AN: 10564

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47065 AN: 68004

Other (OTH) AF: 0.701 AC: 1482 AN: 2114

Alfa AF: 0.703 Hom.: 6396

Bravo AF: 0.733

Asia WGS AF: 0.556 AC: 1939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.75
PhyloP100		-0.33
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: rs1965805; hg19: chr8-73655462;