chr3-178505951-G-C

Variant names:

• chr3-178505951-G-C
• rs1372397
• ENST00000614557.1:c.-68+86576G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000614557.1(ENSG00000275163):​c.-68+86576G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,072 control chromosomes in the GnomAD database, including 12,625 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 0.37 (12625 hom., cov: 33)
• Consequence: ENSG00000275163 ENST00000614557.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.508
• Publications: 2 publications found

Genes affected

ENSG00000275163 (HGNC:):

KCNMB2 (HGNC:6286): (potassium calcium-activated channel subfamily M regulatory beta subunit 2) 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 modulatory beta subunit. The protein encoded by this gene is an auxiliary beta subunit which decreases the activation time of MaxiK alpha subunit currents. Alternative splicing results in multiple transcript variants of this gene. Additional variants are discussed in the literature, but their full length nature has not been described. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000275163	ENST00000614557.1	c.-68+86576G>C		intron_variant	Intron 1 of 4	2		ENSP00000483415.1
KCNMB2	ENST00000437510.5	c.-68+232945G>C		intron_variant	Intron 1 of 3	4		ENSP00000395807.1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56927 AN: 151954 Hom.: 12615 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.374 AC: 56945 AN: 152072 Hom.: 12625 Cov.: 33 AF XY: 0.382 AC XY: 28350 AN XY: 74312

African (AFR) AF: 0.124 AC: 5137 AN: 41514

American (AMR) AF: 0.499 AC: 7619 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1242 AN: 3472

East Asian (EAS) AF: 0.374 AC: 1927 AN: 5158

South Asian (SAS) AF: 0.469 AC: 2257 AN: 4816

European-Finnish (FIN) AF: 0.515 AC: 5427 AN: 10546

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 32017 AN: 67972

Other (OTH) AF: 0.404 AC: 853 AN: 2114

Alfa AF: 0.283 Hom.: 822

Bravo AF: 0.362

Asia WGS AF: 0.461 AC: 1607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.8
DANN	Benign	0.69
PhyloP100		0.51

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: rs1372397; hg19: chr3-178223739;