rs7269864

chr20-49480071-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004975.4(KCNB1):c.567+1843A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,200 control chromosomes in the GnomAD database, including 2,329 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 0.17 (2329 hom., cov: 32)
• Consequence: KCNB1 NM_004975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260

Genes affected

KCNB1 (HGNC:6231): (potassium voltage-gated channel subfamily B member 1) 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 and its activity is modulated by some other family members. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNB1	NM_004975.4	c.567+1843A>G		intron_variant		ENST00000371741.6
KCNB1	XM_011528799.3	c.567+1843A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNB1	ENST00000371741.6	c.567+1843A>G		intron_variant		1	NM_004975.4	P1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26113 AN: 152082 Hom.: 2325 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.172 AC: 26130 AN: 152200 Hom.: 2329 Cov.: 32 AF XY: 0.175 AC XY: 13019 AN XY: 74404

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.158

Alfa AF: 0.173 Hom.: 290

Bravo AF: 0.162

Asia WGS AF: 0.174 AC: 602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	7.5
Dann	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs7269864; hg19: chr20-48096608;