4-109688635-C-T

Position:

• chr4-109688635-C-T

Variant summary

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

The NM_017918.5(MCUB):​c.*1043C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 151,990 control chromosomes in the GnomAD database, including 35,178 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 0.68 (35178 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: MCUB NM_017918.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415

Genes affected

MCUB (HGNC:26076): (mitochondrial calcium uniporter dominant negative subunit beta) Predicted to enable calcium channel inhibitor activity. Predicted to be involved in calcium import into the mitochondrion and mitochondrial calcium ion homeostasis. Located in mitochondrion and nucleoplasm. Is integral component of mitochondrial inner membrane. Part of uniplex complex. [provided by Alliance of Genome Resources, Apr 2022]

CASP6 (HGNC:1507): (caspase 6) This gene encodes a member of the cysteine-aspartic acid protease (caspase) family of enzymes. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic acid residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation cascade. Alternative splicing of this gene results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Oct 2015]

CASP6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCUB	NM_017918.5	c.*1043C>T		3_prime_UTR_variant	8/8	ENST00000394650.7	NP_060388.2
CASP6	NM_001226.4	c.*695G>A		3_prime_UTR_variant	7/7	ENST00000265164.7	NP_001217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCUB	ENST00000394650.7	c.*1043C>T		3_prime_UTR_variant	8/8	1	NM_017918.5	ENSP00000378145.4
CASP6	ENST00000265164	c.*695G>A		3_prime_UTR_variant	7/7	1	NM_001226.4	ENSP00000265164.2
CASP6	ENST00000352981	c.*695G>A		3_prime_UTR_variant	4/4	1		ENSP00000285333.3

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102775 AN: 151874 Hom.: 35136 Cov.: 33

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.659

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.677 AC: 102871 AN: 151990 Hom.: 35178 Cov.: 33 AF XY: 0.672 AC XY: 49905 AN XY: 74310

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.681

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.662

Gnomad4 OTH AF: 0.658

Alfa AF: 0.669 Hom.: 10491

Bravo AF: 0.677

Asia WGS AF: 0.616 AC: 2125 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.6
DANN	Benign	0.68

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: rs3182325; hg19: chr4-110609791; COSMIC: COSV54462128; COSMIC: COSV54462128;