4-109642482-T-C

Variant names:

• chr4-109642482-T-C
• rs1008326
• NM_017918.5:c.100-16529T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017918.5(MCUB):​c.100-16529T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,034 control chromosomes in the GnomAD database, including 21,194 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 0.52 (21194 hom., cov: 32)
• Consequence: MCUB NM_017918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562
• Publications: 3 publications found

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]

ENSG00000304311 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017918.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCUB	NM_017918.5	MANE Select	c.100-16529T>C		intron	N/A	NP_060388.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCUB	ENST00000394650.7	TSL:1 MANE Select	c.100-16529T>C		intron	N/A	ENSP00000378145.4
	MCUB	ENST00000472310.5	TSL:1	n.229-16529T>C		intron	N/A
	MCUB	ENST00000452915.3	TSL:5	n.29-6002T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79350 AN: 151916 Hom.: 21175 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.522 AC: 79432 AN: 152034 Hom.: 21194 Cov.: 32 AF XY: 0.520 AC XY: 38674 AN XY: 74328

African (AFR) AF: 0.438 AC: 18156 AN: 41464

American (AMR) AF: 0.538 AC: 8228 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1668 AN: 3466

East Asian (EAS) AF: 0.483 AC: 2502 AN: 5178

South Asian (SAS) AF: 0.611 AC: 2942 AN: 4816

European-Finnish (FIN) AF: 0.494 AC: 5218 AN: 10568

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38834 AN: 67954

Other (OTH) AF: 0.538 AC: 1130 AN: 2102

Alfa AF: 0.549 Hom.: 8920

Bravo AF: 0.520

Asia WGS AF: 0.556 AC: 1930 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	16
DANN	Benign	0.85
PhyloP100		0.56
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: rs1008326; hg19: chr4-110563638;