rs12317962

Positions:

• chr12-70398802-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.337-1407G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,948 control chromosomes in the GnomAD database, including 5,392 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 0.26 (5392 hom., cov: 32)
• Consequence: KCNMB4 NM_014505.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMB4	NM_014505.6	c.337-1407G>T		intron_variant		ENST00000258111.5	NP_055320.4
KCNMB4	XM_011538188.3	c.337-1407G>T		intron_variant			XP_011536490.1
KCNMB4	XM_047428701.1	c.337-1407G>T		intron_variant			XP_047284657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMB4	ENST00000258111.5	c.337-1407G>T		intron_variant		1	NM_014505.6	ENSP00000258111.4

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38924 AN: 151830 Hom.: 5390 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.256 AC: 38956 AN: 151948 Hom.: 5392 Cov.: 32 AF XY: 0.259 AC XY: 19233 AN XY: 74300

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.272

Alfa AF: 0.225 Hom.: 1911

Bravo AF: 0.267

Asia WGS AF: 0.439 AC: 1525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.49

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: rs12317962; hg19: chr12-70792582;