rs1004256

Positions:

• chr10-72445171-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001195518.2(MICU1):​c.934-21800C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,038 control chromosomes in the GnomAD database, including 23,202 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 0.53 (23202 hom., cov: 32)
• Consequence: MICU1 NM_001195518.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

Genes affected

MICU1 (HGNC:1530): (mitochondrial calcium uptake 1) This gene encodes an essential regulator of mitochondrial Ca2+ uptake under basal conditions. The encoded protein interacts with the mitochondrial calcium uniporter, a mitochondrial inner membrane Ca2+ channel, and is essential in preventing mitochondrial Ca2+ overload, which can cause excessive production of reactive oxygen species and cell stress. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Mar 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICU1	NM_001195518.2	c.934-21800C>T		intron_variant		ENST00000361114.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICU1	ENST00000361114.10	c.934-21800C>T		intron_variant		1	NM_001195518.2	P4

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80722 AN: 151920 Hom.: 23207 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.0374

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.531 AC: 80735 AN: 152038 Hom.: 23202 Cov.: 32 AF XY: 0.517 AC XY: 38435 AN XY: 74302

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.0372

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.542

Alfa AF: 0.629 Hom.: 29289

Bravo AF: 0.520

Asia WGS AF: 0.247 AC: 862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.6
DANN	Benign	0.43

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: rs1004256; hg19: chr10-74204929;