rs6786049

Positions:

• chr3-179241356-C-T

Variant summary

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

The ENST00000485523.5(KCNMB3):​c.*1548G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 154,220 control chromosomes in the GnomAD database, including 526 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 0.079 (506 hom., cov: 32)
  • Exomes 𝑓: 0.11 (20 hom.)
• Consequence: KCNMB3 ENST00000485523.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130

Genes affected

KCNMB3 (HGNC:6287): (potassium calcium-activated channel subfamily M regulatory beta subunit 3) 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 may partially inactivate or slightly decrease the activation time of MaxiK alpha subunit currents. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 22. [provided by RefSeq, Jul 2009]

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 (AFR) allele frequency at 95% confidence interval = 0.0999 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMB3	NM_001163677.2	c.454-1292G>A		intron_variant			NP_001157149.1
KCNMB3	NR_028135.2	n.1812-1292G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMB3	ENST00000485523.5	c.*1548G>A		3_prime_UTR_variant	4/4	1		ENSP00000418536	A2
KCNMB3	ENST00000392686.6	c.*96-1292G>A		intron_variant, NMD_transcript_variant		1		ENSP00000376452
KCNMB3	ENST00000486944.2	c.153-1292G>A		intron_variant		3		ENSP00000479162
KCNMB3	ENST00000497599.5	c.454-1292G>A		intron_variant		2		ENSP00000417091

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 12027 AN: 151980 Hom.: 506 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0910

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.0981

Gnomad SAS AF: 0.0811

Gnomad FIN AF: 0.0682

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.0692

GnomAD4 exome AF: 0.115 AC: 243 AN: 2122 Hom.: 20 Cov.: 0 AF XY: 0.120 AC XY: 127 AN XY: 1062

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.0543

Gnomad4 NFE exome AF: 0.0920

Gnomad4 OTH exome AF: 0.0904

GnomAD4 genome AF: 0.0792 AC: 12047 AN: 152098 Hom.: 506 Cov.: 32 AF XY: 0.0803 AC XY: 5971 AN XY: 74370

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0920

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.0980

Gnomad4 SAS AF: 0.0809

Gnomad4 FIN AF: 0.0682

Gnomad4 NFE AF: 0.0636

Gnomad4 OTH AF: 0.0685

Alfa AF: 0.0730 Hom.: 90

Bravo AF: 0.0834

Asia WGS AF: 0.0790 AC: 274 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6786049; hg19: chr3-178959144; COSMIC: COSV55979537; COSMIC: COSV55979537;