rs992353

Positions:

• chr3-156538672-C-T

Variant summary

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

The ENST00000302490.12(KCNAB1):​c.*1925C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,084 control chromosomes in the GnomAD database, including 23,332 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 0.55 (23332 hom., cov: 34)
  • Failed GnomAD Quality Control
• Consequence: KCNAB1 ENST00000302490.12 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNAB1	NM_001308217.1	c.*1925C>T		3_prime_UTR_variant	13/13		NP_001295146.1
KCNAB1	NM_001308222.1	c.*1925C>T		3_prime_UTR_variant	13/13		NP_001295151.1
KCNAB1	NM_003471.3	c.*1925C>T		3_prime_UTR_variant	14/14		NP_003462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNAB1	ENST00000302490.12	c.*1925C>T		3_prime_UTR_variant	14/14	1		ENSP00000305858	P1
	ENST00000661961.1	n.39-792C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84253 AN: 151966 Hom.: 23333 Cov.: 34

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.538

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.554 AC: 84273 AN: 152084 Hom.: 23332 Cov.: 34 AF XY: 0.552 AC XY: 41058 AN XY: 74324

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.534

Alfa AF: 0.558 Hom.: 7005

Bravo AF: 0.558

Asia WGS AF: 0.531 AC: 1844 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.23
DANN	Benign	0.47

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: rs992353; hg19: chr3-156256461;