4-109657590-T-A

Variant names:

• chr4-109657590-T-A
• rs7690921
• NM_017918.5:c.100-1421T>A

Variant summary

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

The NM_017918.5(MCUB):​c.100-1421T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,196 control chromosomes in the GnomAD database, including 43,353 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 0.75 (43353 hom., cov: 33)
• Consequence: MCUB NM_017918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 4 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 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.100-1421T>A		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.100-1421T>A		intron	N/A	ENSP00000378145.4
	MCUB	ENST00000472310.5	TSL:1	n.229-1421T>A		intron	N/A
	MCUB	ENST00000452915.3	TSL:5	n.195-1421T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113623 AN: 152078 Hom.: 43300 Cov.: 33

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.718

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

GnomAD4 genome AF: 0.747 AC: 113727 AN: 152196 Hom.: 43353 Cov.: 33 AF XY: 0.745 AC XY: 55452 AN XY: 74406

African (AFR) AF: 0.907 AC: 37666 AN: 41550

American (AMR) AF: 0.673 AC: 10289 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2276 AN: 3470

East Asian (EAS) AF: 0.772 AC: 3991 AN: 5172

South Asian (SAS) AF: 0.650 AC: 3121 AN: 4804

European-Finnish (FIN) AF: 0.738 AC: 7808 AN: 10582

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.681 AC: 46336 AN: 68006

Other (OTH) AF: 0.718 AC: 1514 AN: 2110

Alfa AF: 0.720 Hom.: 4955

Bravo AF: 0.750

Asia WGS AF: 0.701 AC: 2440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.73
PhyloP100		0.12
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: rs7690921; hg19: chr4-110578746;