rs9996730

Variant names:

• chr4-109648939-G-T
• rs9996730
• NM_017918.5:c.100-10072G>T

Variant summary

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

The NM_017918.5(MCUB):​c.100-10072G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 151,926 control chromosomes in the GnomAD database, including 38,233 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 0.70 (38233 hom., cov: 30)
• Consequence: MCUB NM_017918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCUB	NM_017918.5	c.100-10072G>T		intron_variant	Intron 1 of 7	ENST00000394650.7	NP_060388.2
MCUB	XM_006714246.4	c.13-10072G>T		intron_variant	Intron 1 of 7		XP_006714309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCUB	ENST00000394650.7	c.100-10072G>T		intron_variant	Intron 1 of 7	1	NM_017918.5	ENSP00000378145.4
MCUB	ENST00000472310.5	n.229-10072G>T		intron_variant	Intron 1 of 4	1
MCUB	ENST00000452915.3	n.194+290G>T		intron_variant	Intron 2 of 5	5
MCUB	ENST00000515114.3	n.226-10072G>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106708 AN: 151808 Hom.: 38167 Cov.: 30

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.703 AC: 106837 AN: 151926 Hom.: 38233 Cov.: 30 AF XY: 0.700 AC XY: 51962 AN XY: 74234

African (AFR) AF: 0.833 AC: 34525 AN: 41454

American (AMR) AF: 0.620 AC: 9476 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2061 AN: 3466

East Asian (EAS) AF: 0.537 AC: 2773 AN: 5162

South Asian (SAS) AF: 0.741 AC: 3562 AN: 4808

European-Finnish (FIN) AF: 0.676 AC: 7117 AN: 10526

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45068 AN: 67918

Other (OTH) AF: 0.682 AC: 1442 AN: 2114

Alfa AF: 0.711 Hom.: 5403

Bravo AF: 0.701

Asia WGS AF: 0.703 AC: 2441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.47
PhyloP100		-0.29
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: rs9996730; hg19: chr4-110570095;