rs992353

Variant names:

• chr3-156538672-C-T
• rs992353
• ENST00000302490.12:c.*1925C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

ENSG00000287916 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KCNAB1	NM_172160.3	c.*1925C>T		downstream_gene_variant		ENST00000490337.6	NP_751892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNAB1	ENST00000302490.12	c.*1925C>T		3_prime_UTR_variant	Exon 14 of 14	1		ENSP00000305858.8
ENSG00000287916	ENST00000661961.1	n.39-792C>T		intron_variant	Intron 1 of 1
KCNAB1	ENST00000490337.6	c.*1925C>T		downstream_gene_variant		1	NM_172160.3	ENSP00000419952.1
KCNAB1	ENST00000471742.5	c.*1925C>T		downstream_gene_variant		1		ENSP00000418956.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.537 AC: 22291 AN: 41488

American (AMR) AF: 0.580 AC: 8866 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1657 AN: 3466

East Asian (EAS) AF: 0.614 AC: 3184 AN: 5182

South Asian (SAS) AF: 0.532 AC: 2566 AN: 4822

European-Finnish (FIN) AF: 0.559 AC: 5889 AN: 10540

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38078 AN: 67984

Other (OTH) AF: 0.534 AC: 1129 AN: 2114

Alfa AF: 0.558 Hom.: 7839

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
PhyloP100		-0.54
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: rs992353; hg19: chr3-156256461;