4-109642482-T-C

Position:

• chr4-109642482-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCUB	NM_017918.5	c.100-16529T>C		intron_variant		ENST00000394650.7	NP_060388.2
MCUB	XM_006714246.4	c.13-16529T>C		intron_variant			XP_006714309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCUB	ENST00000394650.7	c.100-16529T>C		intron_variant		1	NM_017918.5	ENSP00000378145.4
MCUB	ENST00000472310.5	n.229-16529T>C		intron_variant		1
MCUB	ENST00000452915.3	n.29-6002T>C		intron_variant		5
MCUB	ENST00000515114.3	n.226-16529T>C		intron_variant		2

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

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.538

Alfa AF: 0.551 Hom.: 7222

Bravo AF: 0.520

Asia WGS AF: 0.556 AC: 1930 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	16
DANN	Benign	0.85

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: rs1008326; hg19: chr4-110563638;