rs197204

Positions:

• chr4-109576918-C-G
• chr4-109576918-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCUB	NM_017918.5	c.99+16482C>G		intron_variant		ENST00000394650.7	NP_060388.2
MCUB	XM_006714246.4	c.12+15901C>G		intron_variant			XP_006714309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCUB	ENST00000394650.7	c.99+16482C>G		intron_variant		1	NM_017918.5	ENSP00000378145	P1
MCUB	ENST00000472310.5	n.228+16482C>G		intron_variant, non_coding_transcript_variant		1
MCUB	ENST00000452915.3	n.28+15901C>G		intron_variant, non_coding_transcript_variant		5
MCUB	ENST00000515114.3	n.225+16482C>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.529

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.41

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: rs197204; hg19: chr4-110498074;