chr8-72832377-G-A

Variant names:

• chr8-72832377-G-A
• rs17187747
• NM_004770.3:c.580-103558G>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.580-103558G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,950 control chromosomes in the GnomAD database, including 21,217 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 0.52 (21217 hom., cov: 32)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• 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 (NFE) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNB2	NM_004770.3	c.580-103558G>A		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.580-103558G>A		intron_variant	Intron 2 of 2	1	NM_004770.3	ENSP00000430846.1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79086 AN: 151832 Hom.: 21220 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.521 AC: 79117 AN: 151950 Hom.: 21217 Cov.: 32 AF XY: 0.518 AC XY: 38447 AN XY: 74258

African (AFR) AF: 0.396 AC: 16404 AN: 41418

American (AMR) AF: 0.556 AC: 8499 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1981 AN: 3472

East Asian (EAS) AF: 0.392 AC: 2023 AN: 5166

South Asian (SAS) AF: 0.571 AC: 2754 AN: 4820

European-Finnish (FIN) AF: 0.558 AC: 5872 AN: 10520

Middle Eastern (MID) AF: 0.545 AC: 159 AN: 292

European-Non Finnish (NFE) AF: 0.585 AC: 39786 AN: 67962

Other (OTH) AF: 0.542 AC: 1143 AN: 2110

Alfa AF: 0.569 Hom.: 12619

Bravo AF: 0.515

Asia WGS AF: 0.509 AC: 1769 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	0.76
DANN	Benign	0.32
PhyloP100		-0.39
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: rs17187747; hg19: chr8-73744612;