chr5-170386840-T-C

Variant names:

• chr5-170386840-T-C
• rs314111
• NM_004137.4:c.-24-1369A>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.-24-1369A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 151,966 control chromosomes in the GnomAD database, including 1,271 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 (1271 hom., cov: 31)
• Consequence: KCNMB1 NM_004137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 4 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=-0.91).
• 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.-24-1369A>G		intron_variant	Intron 1 of 3	ENST00000274629.9	NP_004128.1
KCNIP1	NM_001034838.3	c.88+32876T>C		intron_variant	Intron 1 of 7		NP_001030010.1
KCNIP1	XM_017009407.2	c.88+32876T>C		intron_variant	Intron 2 of 8		XP_016864896.1
KCNIP1	XM_017009408.2	c.88+32876T>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.-24-1369A>G		intron_variant	Intron 1 of 3	1	NM_004137.4	ENSP00000274629.3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18205 AN: 151850 Hom.: 1270 Cov.: 31

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0708

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0845

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.120 AC: 18233 AN: 151966 Hom.: 1271 Cov.: 31 AF XY: 0.120 AC XY: 8918 AN XY: 74300

African (AFR) AF: 0.175 AC: 7244 AN: 41430

American (AMR) AF: 0.123 AC: 1871 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3472

East Asian (EAS) AF: 0.206 AC: 1061 AN: 5154

South Asian (SAS) AF: 0.139 AC: 667 AN: 4812

European-Finnish (FIN) AF: 0.0708 AC: 748 AN: 10568

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

European-Non Finnish (NFE) AF: 0.0845 AC: 5740 AN: 67944

Other (OTH) AF: 0.128 AC: 271 AN: 2110

Alfa AF: 0.100 Hom.: 3580

Bravo AF: 0.127

Asia WGS AF: 0.174 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.65
PhyloP100		-0.076
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: rs314111; hg19: chr5-169813844;