chr12-70423499-A-G

Position:

• chr12-70423499-A-G

Variant summary

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

The NM_014505.6(KCNMB4):​c.465-6986A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 151,566 control chromosomes in the GnomAD database, including 2,597 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 0.17 (2597 hom., cov: 31)
• Consequence: KCNMB4 NM_014505.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.566

Genes affected

KCNMB4 (HGNC:6289): (potassium calcium-activated channel subfamily M regulatory beta subunit 4) 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 slows activation kinetics, leads to steeper calcium sensitivity, and shifts the voltage range of current activation to more negative potentials than does the beta 1 subunit. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMB4	NM_014505.6	c.465-6986A>G		intron_variant		ENST00000258111.5	NP_055320.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMB4	ENST00000258111.5	c.465-6986A>G		intron_variant		1	NM_014505.6	ENSP00000258111.4
KCNMB4	ENST00000531884.1	n.*136+650A>G		intron_variant		2		ENSP00000431137.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25871 AN: 151450 Hom.: 2584 Cov.: 31

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.171 AC: 25900 AN: 151566 Hom.: 2597 Cov.: 31 AF XY: 0.175 AC XY: 12948 AN XY: 74040

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.159

Alfa AF: 0.117 Hom.: 1268

Bravo AF: 0.178

Asia WGS AF: 0.336 AC: 1168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.29

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: rs787931; hg19: chr12-70817279;