4-109576918-C-G

Variant names:

• chr4-109576918-C-G
• rs197204
• NM_017918.5:c.99+16482C>G

Variant summary

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

The NM_017918.5(MCUB):​c.99+16482C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,904 control chromosomes in the GnomAD database, including 20,937 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 (20937 hom., cov: 31)
• Consequence: MCUB NM_017918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759
• Publications: 1 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.637 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.99+16482C>G		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.99+16482C>G		intron	N/A	ENSP00000378145.4
	MCUB	ENST00000472310.5	TSL:1	n.228+16482C>G		intron	N/A
	MCUB	ENST00000867447.1		c.99+16482C>G		intron	N/A	ENSP00000537506.1

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78513 AN: 151786 Hom.: 20925 Cov.: 31

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.517 AC: 78555 AN: 151904 Hom.: 20937 Cov.: 31 AF XY: 0.519 AC XY: 38539 AN XY: 74254

African (AFR) AF: 0.385 AC: 15946 AN: 41416

American (AMR) AF: 0.560 AC: 8560 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1908 AN: 3468

East Asian (EAS) AF: 0.435 AC: 2248 AN: 5172

South Asian (SAS) AF: 0.656 AC: 3157 AN: 4812

European-Finnish (FIN) AF: 0.567 AC: 5965 AN: 10528

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.573 AC: 38921 AN: 67922

Other (OTH) AF: 0.529 AC: 1116 AN: 2110

Alfa AF: 0.553 Hom.: 2847

Bravo AF: 0.505

Asia WGS AF: 0.533 AC: 1852 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.41
PhyloP100		-0.76
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: rs197204; hg19: chr4-110498074;