3-178539774-G-A

Position:

• chr3-178539774-G-A

Variant summary

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

The NM_181361.3(KCNMB2):​c.-68+3063G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 151,990 control chromosomes in the GnomAD database, including 4,873 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 0.23 (4873 hom., cov: 32)
• Consequence: KCNMB2 NM_181361.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.823

Genes affected

KCNMB2 (HGNC:6286): (potassium calcium-activated channel subfamily M regulatory beta subunit 2) MaxiK channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of smooth muscle tone and neuronal excitability. MaxiK channels can be formed by 2 subunits: the pore-forming alpha subunit and the modulatory beta subunit. The protein encoded by this gene is an auxiliary beta subunit which decreases the activation time of MaxiK alpha subunit currents. Alternative splicing results in multiple transcript variants of this gene. Additional variants are discussed in the literature, but their full length nature has not been described. [provided by RefSeq, Jul 2013]

KCNMB2-AS1 (HGNC:51409): (KCNMB2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMB2	NM_181361.3	c.-68+3063G>A		intron_variant		ENST00000452583.6
KCNMB2-AS1	NR_126560.1	n.575-2378C>T		intron_variant, non_coding_transcript_variant
KCNMB2	XM_011512325.3	c.-145+3063G>A		intron_variant
KCNMB2-AS1	NR_126561.1	n.638-13149C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMB2	ENST00000452583.6	c.-68+3063G>A		intron_variant		1	NM_181361.3	P1
KCNMB2-AS1	ENST00000437488.5	n.522-2378C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35485 AN: 151872 Hom.: 4869 Cov.: 32

Gnomad AFR AF: 0.0860

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.234 AC: 35495 AN: 151990 Hom.: 4873 Cov.: 32 AF XY: 0.240 AC XY: 17794 AN XY: 74280

Gnomad4 AFR AF: 0.0858

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.256

Alfa AF: 0.247 Hom.: 615

Bravo AF: 0.222

Asia WGS AF: 0.354 AC: 1237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.50
DANN	Benign	0.65

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: rs9637454; hg19: chr3-178257562;