rs1557372

Positions:

• chr21-41460614-C-T

Variant summary

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

The ENST00000679386.1(MX1):​c.1759-7623C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,940 control chromosomes in the GnomAD database, including 12,267 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 0.40 (12267 hom., cov: 32)
• Consequence: MX1 ENST00000679386.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 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.1759-7623C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60285 AN: 151822 Hom.: 12262 Cov.: 32

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.397 AC: 60323 AN: 151940 Hom.: 12267 Cov.: 32 AF XY: 0.395 AC XY: 29342 AN XY: 74264

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.414

Alfa AF: 0.384 Hom.: 13136

Bravo AF: 0.403

Asia WGS AF: 0.362 AC: 1256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.6
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1557372; hg19: chr21-42832541;