8-72839285-G-A

Variant names:

• chr8-72839285-G-A
• rs6983627
• NM_004770.3:c.580-96650G>A

Variant summary

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

The NM_004770.3(KCNB2):​c.580-96650G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 152,150 control chromosomes in the GnomAD database, including 56,310 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 0.85 (56310 hom., cov: 32)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.742
• Publications: 2 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.931 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB2	NM_004770.3	MANE Select	c.580-96650G>A		intron	N/A	NP_004761.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB2	ENST00000523207.2	TSL:1 MANE Select	c.580-96650G>A		intron	N/A	ENSP00000430846.1

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129708 AN: 152036 Hom.: 56291 Cov.: 32

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.937

Gnomad OTH AF: 0.875

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

GnomAD4 genome AF: 0.853 AC: 129780 AN: 152150 Hom.: 56310 Cov.: 32 AF XY: 0.849 AC XY: 63139 AN XY: 74394

African (AFR) AF: 0.739 AC: 30670 AN: 41478

American (AMR) AF: 0.847 AC: 12956 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 3240 AN: 3472

East Asian (EAS) AF: 0.485 AC: 2504 AN: 5168

South Asian (SAS) AF: 0.845 AC: 4080 AN: 4828

European-Finnish (FIN) AF: 0.910 AC: 9638 AN: 10586

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.937 AC: 63722 AN: 68012

Other (OTH) AF: 0.875 AC: 1847 AN: 2110

Alfa AF: 0.889 Hom.: 7845

Bravo AF: 0.843

Asia WGS AF: 0.704 AC: 2446 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.38
PhyloP100		-0.74
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: rs6983627; hg19: chr8-73751520;