rs1984473

chr3-156093495-A-Gchr3-156093495-A-T

Variant summary

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

The ENST00000472028.5(KCNAB1):c.-100-24716A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 152,038 control chromosomes in the GnomAD database, including 21,137 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 0.49 (21137 hom., cov: 32)
• Consequence: KCNAB1 ENST00000472028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260

Genes affected

KCNAB1 (HGNC:6228): (potassium voltage-gated channel subfamily A regulatory beta subunit 1) Potassium 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, shaker-related subfamily. This member includes distinct isoforms which are encoded by alternatively spliced transcript variants of this gene. Some of these isoforms are beta subunits, which form heteromultimeric complexes with alpha subunits and modulate the activity of the pore-forming alpha subunits. [provided by RefSeq, Apr 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNAB1	ENST00000472028.5	c.-100-24716A>G		intron_variant		4
KCNAB1	ENST00000477912.5	n.46-24716A>G		intron_variant, non_coding_transcript_variant		4
KCNAB1	ENST00000478609.5	n.46-24716A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74513 AN: 151922 Hom.: 21127 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.490 AC: 74543 AN: 152038 Hom.: 21137 Cov.: 32 AF XY: 0.497 AC XY: 36921 AN XY: 74312

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.730

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.519

Alfa AF: 0.536 Hom.: 7043

Bravo AF: 0.489

Asia WGS AF: 0.577 AC: 2006 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.57
Dann	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1984473; hg19: chr3-155811284;