chr5-170386735-G-C

Variant names:

• chr5-170386735-G-C
• rs314112
• NM_004137.4:c.-24-1264C>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.-24-1264C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 151,368 control chromosomes in the GnomAD database, including 1,203 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 0.12 (1203 hom., cov: 31)
• Consequence: KCNMB1 NM_004137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMB1	NM_004137.4	c.-24-1264C>G		intron_variant	Intron 1 of 3	ENST00000274629.9	NP_004128.1
KCNIP1	NM_001034838.3	c.88+32771G>C		intron_variant	Intron 1 of 7		NP_001030010.1
KCNIP1	XM_017009407.2	c.88+32771G>C		intron_variant	Intron 2 of 8		XP_016864896.1
KCNIP1	XM_017009408.2	c.88+32771G>C		intron_variant	Intron 1 of 3		XP_016864897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMB1	ENST00000274629.9	c.-24-1264C>G		intron_variant	Intron 1 of 3	1	NM_004137.4	ENSP00000274629.3

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17845 AN: 151254 Hom.: 1203 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0708

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0844

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.118 AC: 17866 AN: 151368 Hom.: 1203 Cov.: 31 AF XY: 0.118 AC XY: 8741 AN XY: 73926

African (AFR) AF: 0.168 AC: 6936 AN: 41174

American (AMR) AF: 0.122 AC: 1853 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 547 AN: 3466

East Asian (EAS) AF: 0.206 AC: 1061 AN: 5142

South Asian (SAS) AF: 0.138 AC: 656 AN: 4770

European-Finnish (FIN) AF: 0.0708 AC: 741 AN: 10466

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0844 AC: 5724 AN: 67834

Other (OTH) AF: 0.126 AC: 266 AN: 2104

Alfa AF: 0.106 Hom.: 131

Bravo AF: 0.125

Asia WGS AF: 0.173 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.4
DANN	Benign	0.82
PhyloP100		0.36
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: rs314112; hg19: chr5-169813739;