3-156387295-T-G

Variant names:

• chr3-156387295-T-G
• rs7615568
• NM_172160.3:c.276-34321T>G

Variant summary

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

The NM_172160.3(KCNAB1):​c.276-34321T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,806 control chromosomes in the GnomAD database, including 12,157 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 0.34 (12157 hom., cov: 31)
• Consequence: KCNAB1 NM_172160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNAB1	NM_172160.3	c.276-34321T>G		intron_variant	Intron 1 of 13	ENST00000490337.6	NP_751892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNAB1	ENST00000490337.6	c.276-34321T>G		intron_variant	Intron 1 of 13	1	NM_172160.3	ENSP00000419952.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51247 AN: 151688 Hom.: 12099 Cov.: 31

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.0850

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.338 AC: 51358 AN: 151806 Hom.: 12157 Cov.: 31 AF XY: 0.334 AC XY: 24736 AN XY: 74170

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.0844

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.290

Alfa AF: 0.249 Hom.: 1162

Bravo AF: 0.350

Asia WGS AF: 0.214 AC: 745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.069
DANN	Benign	0.38

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: rs7615568; hg19: chr3-156105084;