8-72584353-A-G

Variant names:

• chr8-72584353-A-G
• rs1542709
• NM_004770.3:c.579+16040A>G

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+16040A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 152,028 control chromosomes in the GnomAD database, including 43,351 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 0.75 (43351 hom., cov: 31)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.383
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNB2	NM_004770.3	c.579+16040A>G		intron_variant	Intron 2 of 2	ENST00000523207.2	NP_004761.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNB2	ENST00000523207.2	c.579+16040A>G		intron_variant	Intron 2 of 2	1	NM_004770.3	ENSP00000430846.1

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114438 AN: 151910 Hom.: 43307 Cov.: 31

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.753 AC: 114534 AN: 152028 Hom.: 43351 Cov.: 31 AF XY: 0.752 AC XY: 55905 AN XY: 74308

African (AFR) AF: 0.796 AC: 32997 AN: 41462

American (AMR) AF: 0.787 AC: 12022 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2553 AN: 3470

East Asian (EAS) AF: 0.687 AC: 3539 AN: 5154

South Asian (SAS) AF: 0.603 AC: 2905 AN: 4820

European-Finnish (FIN) AF: 0.747 AC: 7899 AN: 10576

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.739 AC: 50224 AN: 67958

Other (OTH) AF: 0.734 AC: 1544 AN: 2104

Alfa AF: 0.722 Hom.: 17404

Bravo AF: 0.759

Asia WGS AF: 0.699 AC: 2429 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.30
PhyloP100		-0.38
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: rs1542709; hg19: chr8-73496588;