3-156387295-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172160.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNAB1	NM_172160.3	MANE Select	c.276-34321T>G		intron	N/A	NP_751892.1	Q14722-1
	KCNAB1	NM_003471.3		c.243-34321T>G		intron	N/A	NP_003462.2	Q14722-3
	KCNAB1	NM_172159.3		c.222-34321T>G		intron	N/A	NP_751891.1	Q14722-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNAB1	ENST00000490337.6	TSL:1 MANE Select	c.276-34321T>G		intron	N/A	ENSP00000419952.1	Q14722-1
	KCNAB1	ENST00000471742.5	TSL:1	c.243-34321T>G		intron	N/A	ENSP00000418956.1	Q14722-3
	KCNAB1	ENST00000302490.12	TSL:1	c.222-34321T>G		intron	N/A	ENSP00000305858.8	Q14722-2

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

African (AFR) AF: 0.679 AC: 28057 AN: 41318

American (AMR) AF: 0.197 AC: 3013 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 838 AN: 3468

East Asian (EAS) AF: 0.0844 AC: 436 AN: 5164

South Asian (SAS) AF: 0.277 AC: 1328 AN: 4798

European-Finnish (FIN) AF: 0.202 AC: 2132 AN: 10558

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.215 AC: 14635 AN: 67942

Other (OTH) AF: 0.290 AC: 608 AN: 2096

Alfa AF: 0.241 Hom.: 8023

Bravo AF: 0.350

Asia WGS AF: 0.214 AC: 745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.069
DANN	Benign	0.38
PhyloP100		-2.6
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: rs7615568; hg19: chr3-156105084;