3-156239944-A-G

Position:

• chr3-156239944-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.275+119058A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,018 control chromosomes in the GnomAD database, including 41,527 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 0.74 (41527 hom., cov: 30)
• Consequence: KCNAB1 NM_172160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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]

KCNAB1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNAB1	NM_172160.3	c.275+119058A>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.275+119058A>G		intron_variant		1	NM_172160.3	ENSP00000419952.1

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111930 AN: 151900 Hom.: 41474 Cov.: 30

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.737 AC: 112038 AN: 152018 Hom.: 41527 Cov.: 30 AF XY: 0.739 AC XY: 54940 AN XY: 74312

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.757

Gnomad4 EAS AF: 0.901

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.803

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.727

Alfa AF: 0.741 Hom.: 12220

Bravo AF: 0.739

Asia WGS AF: 0.739 AC: 2570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.22
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6775600; hg19: chr3-155957733;