rs716595

chr10-110246728-G-Achr10-110246728-G-T

Variant summary

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

The NM_130439.3(MXI1):c.437+1871G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0881 in 152,200 control chromosomes in the GnomAD database, including 1,105 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 0.088 (1105 hom., cov: 32)
• Consequence: MXI1 NM_130439.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MXI1	NM_130439.3	c.437+1871G>A		intron_variant		ENST00000332674.9
MXI1	NM_001008541.1	c.98+18407G>A		intron_variant
MXI1	NM_005962.5	c.236+1871G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MXI1	ENST00000332674.9	c.437+1871G>A		intron_variant		1	NM_130439.3

Frequencies

GnomAD3 genomes AF: 0.0882 AC: 13407 AN: 152082 Hom.: 1107 Cov.: 32

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.0667

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0776

Gnomad OTH AF: 0.0947

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

GnomAD4 genome AF: 0.0881 AC: 13407 AN: 152200 Hom.: 1105 Cov.: 32 AF XY: 0.0934 AC XY: 6946 AN XY: 74402

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.0667

Gnomad4 NFE AF: 0.0776

Gnomad4 OTH AF: 0.0938

Alfa AF: 0.0874 Hom.: 1233

Bravo AF: 0.101

Asia WGS AF: 0.221 AC: 772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	12
Dann	Benign	0.59

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: rs716595; hg19: chr10-112006486;