rs10488885

Variant names:

• chr4-109662878-C-T
• rs10488885
• NM_017918.5:c.347-1412C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BS1 BS2

The NM_017918.5(MCUB):​c.347-1412C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 151,890 control chromosomes in the GnomAD database, including 32 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 0.017 (32 hom., cov: 32)
• Consequence: MCUB NM_017918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.13).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0169 (2568/151890) while in subpopulation NFE AF = 0.0248 (1688/67964). AF 95% confidence interval is 0.0239. There are 32 homozygotes in GnomAd4. There are 1218 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCUB	NM_017918.5	c.347-1412C>T		intron_variant	Intron 3 of 7	ENST00000394650.7	NP_060388.2
MCUB	XM_006714246.4	c.260-1412C>T		intron_variant	Intron 3 of 7		XP_006714309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCUB	ENST00000394650.7	c.347-1412C>T		intron_variant	Intron 3 of 7	1	NM_017918.5	ENSP00000378145.4
MCUB	ENST00000472310.5	n.476-1412C>T		intron_variant	Intron 3 of 4	1
MCUB	ENST00000452915.3	n.442-1412C>T		intron_variant	Intron 4 of 5	5

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 2568 AN: 151774 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.00472

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0224

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00621

Gnomad FIN AF: 0.0175

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0248

Gnomad OTH AF: 0.0216

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

GnomAD4 genome AF: 0.0169 AC: 2568 AN: 151890 Hom.: 32 Cov.: 32 AF XY: 0.0164 AC XY: 1218 AN XY: 74212

African (AFR) AF: 0.00471 AC: 195 AN: 41404

American (AMR) AF: 0.0224 AC: 341 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00622 AC: 30 AN: 4822

European-Finnish (FIN) AF: 0.0175 AC: 184 AN: 10520

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0248 AC: 1688 AN: 67964

Other (OTH) AF: 0.0214 AC: 45 AN: 2104

Alfa AF: 0.0218 Hom.: 76

Bravo AF: 0.0174

Asia WGS AF: 0.00462 AC: 16 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.13
CADD	Benign	17
DANN	Benign	0.73
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism

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: rs10488885; hg19: chr4-110584034;