rs7645550

Variant names:

• chr3-179250846-C-T
• rs7645550
• NM_171830.2:c.145G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_171830.2(KCNMB3):​c.145G>A​(p.Ala49Thr) variant causes a missense change. The variant allele was found at a frequency of 0.376 in 1,613,814 control chromosomes in the GnomAD database, including 116,715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10431 hom., cov: 32)
  • Exomes 𝑓: 0.38 (106284 hom.)
• Consequence: KCNMB3 NM_171830.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.63
• Publications: 35 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023398757).
• BP6: Variant 3-179250846-C-T is Benign according to our data. Variant chr3-179250846-C-T is described in ClinVar as Benign. ClinVar VariationId is 1250939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_171830.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB3	NM_171830.2	MANE Select	c.145G>A	p.Ala49Thr	missense	Exon 1 of 3	NP_741981.1	Q9NPA1-3
	KCNMB3	NM_014407.3		c.157G>A	p.Ala53Thr	missense	Exon 2 of 4	NP_055222.3	Q9NPA1-1
	KCNMB3	NM_171828.3		c.151G>A	p.Ala51Thr	missense	Exon 2 of 4	NP_741979.1	Q9NPA1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB3	ENST00000392685.7	TSL:1 MANE Select	c.145G>A	p.Ala49Thr	missense	Exon 1 of 3	ENSP00000376451.2	Q9NPA1-3
	KCNMB3	ENST00000314235.9	TSL:1	c.157G>A	p.Ala53Thr	missense	Exon 2 of 4	ENSP00000319370.5	Q9NPA1-1
	KCNMB3	ENST00000485523.5	TSL:1	c.91G>A	p.Ala31Thr	missense	Exon 2 of 4	ENSP00000418536.1	Q9NPA1-4

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55683 AN: 151922 Hom.: 10426 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.367

GnomAD2 exomes AF: 0.343 AC: 86143 AN: 251440 AF XY: 0.344

Gnomad AFR exome AF: 0.380

Gnomad AMR exome AF: 0.287

Gnomad ASJ exome AF: 0.334

Gnomad EAS exome AF: 0.122

Gnomad FIN exome AF: 0.364

Gnomad NFE exome AF: 0.396

Gnomad OTH exome AF: 0.341

GnomAD4 exome AF: 0.377 AC: 551239 AN: 1461774 Hom.: 106284 Cov.: 42 AF XY: 0.375 AC XY: 272789 AN XY: 727204

African (AFR) AF: 0.378 AC: 12659 AN: 33474

American (AMR) AF: 0.291 AC: 13033 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 8794 AN: 26136

East Asian (EAS) AF: 0.101 AC: 4023 AN: 39698

South Asian (SAS) AF: 0.311 AC: 26805 AN: 86256

European-Finnish (FIN) AF: 0.360 AC: 19244 AN: 53420

Middle Eastern (MID) AF: 0.319 AC: 1840 AN: 5766

European-Non Finnish (NFE) AF: 0.399 AC: 443401 AN: 1111906

Other (OTH) AF: 0.355 AC: 21440 AN: 60394

GnomAD4 genome AF: 0.367 AC: 55728 AN: 152040 Hom.: 10431 Cov.: 32 AF XY: 0.363 AC XY: 26960 AN XY: 74328

African (AFR) AF: 0.376 AC: 15573 AN: 41444

American (AMR) AF: 0.323 AC: 4937 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1113 AN: 3468

East Asian (EAS) AF: 0.121 AC: 626 AN: 5180

South Asian (SAS) AF: 0.306 AC: 1475 AN: 4826

European-Finnish (FIN) AF: 0.370 AC: 3909 AN: 10560

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26688 AN: 67958

Other (OTH) AF: 0.364 AC: 768 AN: 2112

Alfa AF: 0.380 Hom.: 50117

Bravo AF: 0.362

TwinsUK AF: 0.404 AC: 1499

ALSPAC AF: 0.401 AC: 1546

ESP6500AA AF: 0.388 AC: 1710

ESP6500EA AF: 0.382 AC: 3284

ExAC AF: 0.346 AC: 41962

Asia WGS AF: 0.211 AC: 734 AN: 3478

EpiCase AF: 0.391

EpiControl AF: 0.388

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.071	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.83	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		4.6
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.21
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.037	D
Polyphen		0.99	D
Vest4		0.33
MPC		0.36
ClinPred		0.028	T
GERP RS		6.1
PromoterAI		0.00010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.097
gMVP		0.33
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7645550; hg19: chr3-178968634; COSMIC: COSV58570199;