3-178304602-A-G

Position:

• chr3-178304602-A-G

Variant summary

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

The ENST00000651749.1(ENSG00000223930):​n.143+67149T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 152,046 control chromosomes in the GnomAD database, including 32,839 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 0.65 (32839 hom., cov: 32)
• Consequence: ENST00000651749.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.692

Genes affected

(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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105374235	XR_001741029.2	n.157-26545T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000651749.1	n.143+67149T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99198 AN: 151928 Hom.: 32807 Cov.: 32

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.653 AC: 99275 AN: 152046 Hom.: 32839 Cov.: 32 AF XY: 0.651 AC XY: 48422 AN XY: 74332

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.671

Alfa AF: 0.614 Hom.: 59517

Bravo AF: 0.656

Asia WGS AF: 0.475 AC: 1645 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.17
DANN	Benign	0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6791314; hg19: chr3-178022390;