5-170386292-T-G

Position:

• chr5-170386292-T-G

Variant summary

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

The NM_004137.4(KCNMB1):​c.-24-821A>C 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 151,950 control chromosomes in the GnomAD database, including 1,190 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 (1190 hom., cov: 32)
• Consequence: KCNMB1 NM_004137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMB1	NM_004137.4	c.-24-821A>C		intron_variant		ENST00000274629.9	NP_004128.1
KCNIP1	NM_001034838.3	c.88+32328T>G		intron_variant			NP_001030010.1
KCNIP1	XM_017009407.2	c.88+32328T>G		intron_variant			XP_016864896.1
KCNIP1	XM_017009408.2	c.88+32328T>G		intron_variant			XP_016864897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMB1	ENST00000274629.9	c.-24-821A>C		intron_variant		1	NM_004137.4	ENSP00000274629.3

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17854 AN: 151832 Hom.: 1190 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0711

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0847

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: 17872 AN: 151950 Hom.: 1190 Cov.: 32 AF XY: 0.118 AC XY: 8780 AN XY: 74268

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.0711

Gnomad4 NFE AF: 0.0847

Gnomad4 OTH AF: 0.127

Alfa AF: 0.0693 Hom.: 102

Bravo AF: 0.124

Asia WGS AF: 0.176 AC: 612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.30
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs314113; hg19: chr5-169813296;