12-70433999-G-T

Variant names:

• chr12-70433999-G-T
• rs398702
• NM_014505.6:c.*3346G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KCNMB4	NM_014505.6	c.*3346G>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000258111.5	NP_055320.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMB4	ENST00000258111.5	c.*3346G>T		3_prime_UTR_variant	Exon 3 of 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

African (AFR) AF: 1.00 AC: 4 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.909 AC: 20 AN: 22

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.970 AC: 40330 AN: 41566

American (AMR) AF: 0.888 AC: 13580 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2923 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5162 AN: 5166

South Asian (SAS) AF: 0.952 AC: 4592 AN: 4822

European-Finnish (FIN) AF: 0.891 AC: 9442 AN: 10600

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57100 AN: 68012

Other (OTH) AF: 0.885 AC: 1872 AN: 2116

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
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs398702; hg19: chr12-70827779;