rs1450111

Positions:

• chr3-156367041-A-G

Variant summary

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

The NM_172160.3(KCNAB1):​c.276-54575A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,116 control chromosomes in the GnomAD database, including 7,143 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 0.27 (7143 hom., cov: 32)
• Consequence: KCNAB1 NM_172160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.565

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNAB1	NM_172160.3	c.276-54575A>G		intron_variant		ENST00000490337.6	NP_751892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNAB1	ENST00000490337.6	c.276-54575A>G		intron_variant		1	NM_172160.3	ENSP00000419952
	ENST00000661961.1	n.39-172423A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41229 AN: 151998 Hom.: 7121 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.0509

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.271 AC: 41294 AN: 152116 Hom.: 7143 Cov.: 32 AF XY: 0.266 AC XY: 19807 AN XY: 74370

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.0511

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.252

Alfa AF: 0.281 Hom.: 1027

Bravo AF: 0.280

Asia WGS AF: 0.140 AC: 488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.8
DANN	Benign	0.63

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: rs1450111; hg19: chr3-156084830;