12-70433999-G-T

Position:

• chr12-70433999-G-T

Variant summary

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

The NM_014505.6(KCNMB4):​c.*3346G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 152,280 control chromosomes in the GnomAD database, including 60,890 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 0.89 (60878 hom., cov: 32)
  • Exomes 𝑓: 0.93 (12 hom.)
• Consequence: KCNMB4 NM_014505.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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 = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMB4	NM_014505.6	c.*3346G>T		3_prime_UTR_variant	3/3	ENST00000258111.5	NP_055320.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMB4	ENST00000258111.5	c.*3346G>T		3_prime_UTR_variant	3/3	1	NM_014505.6	ENSP00000258111.4

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135682 AN: 152134 Hom.: 60819 Cov.: 32

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.883

GnomAD4 exome AF: 0.929 AC: 26 AN: 28 Hom.: 12 Cov.: 0 AF XY: 0.909 AC XY: 20 AN XY: 22

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 NFE exome AF: 0.909

GnomAD4 genome AF: 0.892 AC: 135800 AN: 152252 Hom.: 60878 Cov.: 32 AF XY: 0.896 AC XY: 66676 AN XY: 74432

Gnomad4 AFR AF: 0.970

Gnomad4 AMR AF: 0.888

Gnomad4 ASJ AF: 0.842

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.952

Gnomad4 FIN AF: 0.891

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.885

Alfa AF: 0.874 Hom.: 9225

Bravo AF: 0.895

Asia WGS AF: 0.975 AC: 3391 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	0.44
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs398702; hg19: chr12-70827779;