rs13433394

Positions:

• chr21-41459983-C-T

Variant summary

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

The ENST00000679386.1(MX1):​c.1758+7114C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,042 control chromosomes in the GnomAD database, including 4,379 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 0.22 (4379 hom., cov: 32)
• Consequence: MX1 ENST00000679386.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

Genes affected

MX1 (HGNC:7532): (MX dynamin like GTPase 1) This gene encodes a guanosine triphosphate (GTP)-metabolizing protein that participates in the cellular antiviral response. The encoded protein is induced by type I and type II interferons and antagonizes the replication process of several different RNA and DNA viruses. There is a related gene located adjacent to this gene on chromosome 21, and there are multiple pseudogenes located in a cluster on chromosome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MX1	ENST00000679386.1	c.1758+7114C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33418 AN: 151924 Hom.: 4368 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.220 AC: 33472 AN: 152042 Hom.: 4379 Cov.: 32 AF XY: 0.224 AC XY: 16659 AN XY: 74306

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.0956

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.177

Alfa AF: 0.191 Hom.: 646

Bravo AF: 0.214

Asia WGS AF: 0.304 AC: 1060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13433394; hg19: chr21-42831910;