chr5-170387428-T-C

Position:

• chr5-170387428-T-C

Variant summary

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

The NM_004137.4(KCNMB1):​c.-25+1831A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,104 control chromosomes in the GnomAD database, including 1,606 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 0.13 (1606 hom., cov: 32)
• Consequence: KCNMB1 NM_004137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175

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]

KCNIP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMB1	NM_004137.4	c.-25+1831A>G		intron_variant		ENST00000274629.9	NP_004128.1
KCNIP1	NM_001034838.3	c.88+33464T>C		intron_variant			NP_001030010.1
KCNIP1	XM_017009407.2	c.88+33464T>C		intron_variant			XP_016864896.1
KCNIP1	XM_017009408.2	c.88+33464T>C		intron_variant			XP_016864897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMB1	ENST00000274629.9	c.-25+1831A>G		intron_variant		1	NM_004137.4	ENSP00000274629.3

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20245 AN: 151984 Hom.: 1602 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0704

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.0845

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.133 AC: 20288 AN: 152104 Hom.: 1606 Cov.: 32 AF XY: 0.133 AC XY: 9908 AN XY: 74354

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.0704

Gnomad4 NFE AF: 0.0845

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0389 Hom.: 34

Bravo AF: 0.143

Asia WGS AF: 0.179 AC: 621 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	2.7
DANN	Benign	0.61

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: rs314109; hg19: chr5-169814432;