5-170378626-G-T

Variant names:

• chr5-170378626-G-T
• rs2656842
• NM_004137.4:c.*78C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004137.4(KCNMB1):​c.*78C>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 0.3 in 1,437,590 control chromosomes in the GnomAD database, including 68,114 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 0.35 (9532 hom., cov: 33)
  • Exomes 𝑓: 0.29 (58582 hom.)
• Consequence: KCNMB1 NM_004137.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 10 publications found

Genes affected

KCNMB1 (HGNC:6285): (potassium calcium-activated channel subfamily M regulatory beta subunit 1) 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 product of this gene, the modulatory beta subunit. Intracellular calcium regulates the physical association between the alpha and beta subunits. [provided by RefSeq, Jul 2008]

KCNIP1 (HGNC:15521): (potassium voltage-gated channel interacting protein 1) This gene encodes a member of the family of cytosolic voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belong to the neuronal calcium sensor (NCS) family of the calcium binding EF-hand proteins. They associate with Kv4 alpha subunits to form native Kv4 channel complexes. The encoded protein may regulate rapidly inactivating (A-type) currents, and hence neuronal membrane excitability, in response to changes in the concentration of intracellular calcium. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004137.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB1	NM_004137.4	MANE Select	c.*78C>A		3_prime_UTR	Exon 4 of 4	NP_004128.1
	KCNIP1	NM_001034838.3		c.88+24662G>T		intron	N/A	NP_001030010.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB1	ENST00000274629.9	TSL:1 MANE Select	c.*78C>A		3_prime_UTR	Exon 4 of 4	ENSP00000274629.3
	KCNIP1	ENST00000377360.8	TSL:1	c.88+24662G>T		intron	N/A	ENSP00000366577.4
	KCNIP1	ENST00000517344.1	TSL:3	n.88+24662G>T		intron	N/A	ENSP00000431053.1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52368 AN: 151776 Hom.: 9524 Cov.: 33

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.343

GnomAD4 exome AF: 0.295 AC: 378855 AN: 1285696 Hom.: 58582 Cov.: 20 AF XY: 0.297 AC XY: 188985 AN XY: 635526

African (AFR) AF: 0.474 AC: 13561 AN: 28622

American (AMR) AF: 0.345 AC: 10260 AN: 29732

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 5248 AN: 19502

East Asian (EAS) AF: 0.375 AC: 14480 AN: 38580

South Asian (SAS) AF: 0.405 AC: 27883 AN: 68806

European-Finnish (FIN) AF: 0.249 AC: 11663 AN: 46900

Middle Eastern (MID) AF: 0.374 AC: 1725 AN: 4614

European-Non Finnish (NFE) AF: 0.279 AC: 277426 AN: 995230

Other (OTH) AF: 0.309 AC: 16609 AN: 53710

GnomAD4 genome AF: 0.345 AC: 52411 AN: 151894 Hom.: 9532 Cov.: 33 AF XY: 0.345 AC XY: 25608 AN XY: 74252

African (AFR) AF: 0.465 AC: 19223 AN: 41382

American (AMR) AF: 0.355 AC: 5418 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 902 AN: 3470

East Asian (EAS) AF: 0.345 AC: 1781 AN: 5162

South Asian (SAS) AF: 0.417 AC: 2005 AN: 4808

European-Finnish (FIN) AF: 0.240 AC: 2541 AN: 10568

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19608 AN: 67914

Other (OTH) AF: 0.339 AC: 716 AN: 2112

Alfa AF: 0.279 Hom.: 2301

Bravo AF: 0.352

Asia WGS AF: 0.387 AC: 1345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.025
DANN	Benign	0.43
PhyloP100		-1.3
Mutation Taster		=100/0	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: rs2656842; hg19: chr5-169805630; COSMIC: COSV51131768; COSMIC: COSV51131768;