rs2280807

Positions:

• chr21-41449338-A-G
• chr21-41449338-A-T

Variant summary

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

The NM_002462.5(MX1):​c.1432+43A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,574,100 control chromosomes in the GnomAD database, including 17,581 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 0.16 (2185 hom., cov: 31)
  • Exomes 𝑓: 0.14 (15396 hom.)
• Consequence: MX1 NM_002462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.919

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]

MX1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MX1	NM_002462.5	c.1432+43A>G		intron_variant		ENST00000398598.8	NP_002453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MX1	ENST00000398598.8	c.1432+43A>G		intron_variant		1	NM_002462.5	ENSP00000381599.3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24516 AN: 151960 Hom.: 2178 Cov.: 31

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0806

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.143

GnomAD3 exomes AF: 0.171 AC: 37347 AN: 218126 Hom.: 3579 AF XY: 0.167 AC XY: 19764 AN XY: 118424

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.238

Gnomad ASJ exome AF: 0.0867

Gnomad EAS exome AF: 0.280

Gnomad SAS exome AF: 0.176

Gnomad FIN exome AF: 0.201

Gnomad NFE exome AF: 0.133

Gnomad OTH exome AF: 0.163

GnomAD4 exome AF: 0.141 AC: 199914 AN: 1422022 Hom.: 15396 Cov.: 30 AF XY: 0.141 AC XY: 99330 AN XY: 704788

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.0869

Gnomad4 EAS exome AF: 0.291

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.161 AC: 24555 AN: 152078 Hom.: 2185 Cov.: 31 AF XY: 0.166 AC XY: 12330 AN XY: 74340

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.0806

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.142

Alfa AF: 0.136 Hom.: 2600

Bravo AF: 0.161

Asia WGS AF: 0.207 AC: 720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.54

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: rs2280807; hg19: chr21-42821265; COSMIC: COSV55819402; COSMIC: COSV55819402;