rs2253667

Variant names:

• chr8-72740413-G-A
• rs2253667
• NM_004770.3:c.579+172100G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-72740413-G-A
• chr8-72740413-G-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+172100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,066 control chromosomes in the GnomAD database, including 3,382 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 0.18 (3382 hom., cov: 32)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 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+172100G>A		intron	N/A	NP_004761.2
	LOC101926908	NR_110656.1		n.57+8312G>A		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+172100G>A		intron	N/A	ENSP00000430846.1	Q92953
	ENSG00000253726	ENST00000519427.1	TSL:2	n.57+8312G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27882 AN: 151948 Hom.: 3373 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.184 AC: 27927 AN: 152066 Hom.: 3382 Cov.: 32 AF XY: 0.183 AC XY: 13635 AN XY: 74358

African (AFR) AF: 0.342 AC: 14182 AN: 41462

American (AMR) AF: 0.116 AC: 1765 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3470

East Asian (EAS) AF: 0.210 AC: 1085 AN: 5164

South Asian (SAS) AF: 0.178 AC: 858 AN: 4820

European-Finnish (FIN) AF: 0.148 AC: 1567 AN: 10584

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7455 AN: 67982

Other (OTH) AF: 0.169 AC: 356 AN: 2104

Alfa AF: 0.151 Hom.: 306

Bravo AF: 0.189

Asia WGS AF: 0.209 AC: 728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.76
PhyloP100		-0.21
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: rs2253667; hg19: chr8-73652648;