5-170378407-T-C

Variant names:

• chr5-170378407-T-C
• rs314156
• NM_004137.4:c.*297A>G

Variant summary

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

The NM_004137.4(KCNMB1):​c.*297A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 335,132 control chromosomes in the GnomAD database, including 2,813 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 0.14 (1699 hom., cov: 32)
  • Exomes 𝑓: 0.098 (1114 hom.)
• Consequence: KCNMB1 NM_004137.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB1	NM_004137.4	MANE Select	c.*297A>G		3_prime_UTR	Exon 4 of 4	NP_004128.1	Q16558-1
	KCNIP1	NM_001034838.3		c.88+24443T>C		intron	N/A	NP_001030010.1	Q9NZI2-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB1	ENST00000274629.9	TSL:1 MANE Select	c.*297A>G		3_prime_UTR	Exon 4 of 4	ENSP00000274629.3	Q16558-1
	KCNIP1	ENST00000377360.8	TSL:1	c.88+24443T>C		intron	N/A	ENSP00000366577.4	Q9NZI2-4
	KCNMB1	ENST00000962422.1		c.*297A>G		3_prime_UTR	Exon 4 of 4	ENSP00000632481.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20497 AN: 151912 Hom.: 1690 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0601

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.0867

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.0980 AC: 17937 AN: 183102 Hom.: 1114 Cov.: 0 AF XY: 0.0983 AC XY: 9105 AN XY: 92640

African (AFR) AF: 0.228 AC: 1302 AN: 5708

American (AMR) AF: 0.144 AC: 989 AN: 6884

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 945 AN: 6554

East Asian (EAS) AF: 0.130 AC: 1801 AN: 13848

South Asian (SAS) AF: 0.107 AC: 971 AN: 9104

European-Finnish (FIN) AF: 0.0527 AC: 558 AN: 10586

Middle Eastern (MID) AF: 0.214 AC: 204 AN: 954

European-Non Finnish (NFE) AF: 0.0839 AC: 9846 AN: 117420

Other (OTH) AF: 0.110 AC: 1321 AN: 12044

GnomAD4 genome AF: 0.135 AC: 20536 AN: 152030 Hom.: 1699 Cov.: 32 AF XY: 0.135 AC XY: 9999 AN XY: 74322

African (AFR) AF: 0.234 AC: 9709 AN: 41422

American (AMR) AF: 0.137 AC: 2098 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 524 AN: 3466

East Asian (EAS) AF: 0.126 AC: 651 AN: 5168

South Asian (SAS) AF: 0.132 AC: 636 AN: 4806

European-Finnish (FIN) AF: 0.0601 AC: 637 AN: 10592

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.0867 AC: 5894 AN: 67982

Other (OTH) AF: 0.144 AC: 304 AN: 2112

Alfa AF: 0.112 Hom.: 1471

Bravo AF: 0.144

Asia WGS AF: 0.155 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.31
DANN	Benign	0.45
PhyloP100		-1.7
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: rs314156; hg19: chr5-169805411;