rs1418362

Positions:

• chr10-110243884-T-A

Variant summary

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

The NM_130439.3(MXI1):​c.408-944T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 151,958 control chromosomes in the GnomAD database, including 2,997 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 0.19 (2997 hom., cov: 32)
• Consequence: MXI1 NM_130439.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

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=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MXI1	NM_130439.3	c.408-944T>A		intron_variant		ENST00000332674.9	NP_569157.2
MXI1	NM_005962.5	c.207-944T>A		intron_variant			NP_005953.4
MXI1	NM_001008541.1	c.98+15563T>A		intron_variant			NP_001008541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MXI1	ENST00000332674.9	c.408-944T>A		intron_variant		1	NM_130439.3	ENSP00000331152.5

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29066 AN: 151840 Hom.: 2988 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0879

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.192 AC: 29107 AN: 151958 Hom.: 2997 Cov.: 32 AF XY: 0.187 AC XY: 13911 AN XY: 74278

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.0878

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.202

Alfa AF: 0.189 Hom.: 353

Bravo AF: 0.198

Asia WGS AF: 0.174 AC: 608 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.1
DANN	Benign	0.83

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: rs1418362; hg19: chr10-112003642;