rs11195062

Variant names:

• chr10-110277217-C-A
• rs11195062
• NM_130439.3:c.438-1963C>A

Variant summary

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

The ENST00000332674.9(MXI1):​c.438-1963C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,040 control chromosomes in the GnomAD database, including 13,715 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 0.41 (13715 hom., cov: 32)
• Consequence: MXI1 ENST00000332674.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.692
• Publications: 16 publications found

Genes affected

MXI1 (HGNC:7534): (MAX interactor 1, dimerization protein) Expression of the c-myc gene, which produces an oncogenic transcription factor, is tightly regulated in normal cells but is frequently deregulated in human cancers. The protein encoded by this gene is a transcriptional repressor thought to negatively regulate MYC function, and is therefore a potential tumor suppressor. This protein inhibits the transcriptional activity of MYC by competing for MAX, another basic helix-loop-helix protein that binds to MYC and is required for its function. Defects in this gene are frequently found in patients with prostate tumors. Three alternatively spliced transcripts encoding different isoforms have been described. Additional alternatively spliced transcripts may exist but the products of these transcripts have not been verified experimentally. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000332674.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MXI1	NM_130439.3	MANE Select	c.438-1963C>A		intron	N/A	NP_569157.2
	MXI1	NM_005962.5		c.237-1963C>A		intron	N/A	NP_005953.4
	MXI1	NM_001008541.1		c.99-1963C>A		intron	N/A	NP_001008541.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MXI1	ENST00000332674.9	TSL:1 MANE Select	c.438-1963C>A		intron	N/A	ENSP00000331152.5
	MXI1	ENST00000239007.11	TSL:1	c.237-1963C>A		intron	N/A	ENSP00000239007.7
	MXI1	ENST00000361248.8	TSL:1	c.99-1963C>A		intron	N/A	ENSP00000354606.4

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62835 AN: 151922 Hom.: 13703 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.414 AC: 62900 AN: 152040 Hom.: 13715 Cov.: 32 AF XY: 0.421 AC XY: 31266 AN XY: 74346

African (AFR) AF: 0.445 AC: 18455 AN: 41460

American (AMR) AF: 0.508 AC: 7757 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1346 AN: 3470

East Asian (EAS) AF: 0.649 AC: 3361 AN: 5180

South Asian (SAS) AF: 0.703 AC: 3399 AN: 4832

European-Finnish (FIN) AF: 0.324 AC: 3419 AN: 10560

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23843 AN: 67950

Other (OTH) AF: 0.427 AC: 900 AN: 2106

Alfa AF: 0.381 Hom.: 44377

Bravo AF: 0.427

Asia WGS AF: 0.679 AC: 2363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.0
DANN	Benign	0.57
PhyloP100		0.69
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: rs11195062; hg19: chr10-112036975;