rs2280807

Variant names:

• chr21-41449338-A-G
• rs2280807
• NM_002462.5:c.1432+43A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002462.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MX1	NM_002462.5	MANE Select	c.1432+43A>G		intron	N/A	NP_002453.2	P20591-1
	MX1	NM_001144925.2		c.1432+43A>G		intron	N/A	NP_001138397.1	P20591-1
	MX1	NM_001178046.3		c.1432+43A>G		intron	N/A	NP_001171517.1	P20591-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MX1	ENST00000398598.8	TSL:1 MANE Select	c.1432+43A>G		intron	N/A	ENSP00000381599.3	P20591-1
	MX1	ENST00000455164.6	TSL:1	c.1432+43A>G		intron	N/A	ENSP00000410523.2	P20591-1
	MX1	ENST00000896042.1		c.1552+43A>G		intron	N/A	ENSP00000566101.1

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

GnomAD2 exomes AF: 0.171 AC: 37347 AN: 218126 AF XY: 0.167

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 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

African (AFR) AF: 0.196 AC: 6140 AN: 31348

American (AMR) AF: 0.221 AC: 8219 AN: 37108

Ashkenazi Jewish (ASJ) AF: 0.0869 AC: 2115 AN: 24346

East Asian (EAS) AF: 0.291 AC: 11141 AN: 38278

South Asian (SAS) AF: 0.173 AC: 13954 AN: 80588

European-Finnish (FIN) AF: 0.196 AC: 10273 AN: 52466

Middle Eastern (MID) AF: 0.142 AC: 783 AN: 5512

European-Non Finnish (NFE) AF: 0.127 AC: 138889 AN: 1093708

Other (OTH) AF: 0.143 AC: 8400 AN: 58668

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

African (AFR) AF: 0.192 AC: 7957 AN: 41496

American (AMR) AF: 0.154 AC: 2351 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0806 AC: 280 AN: 3472

East Asian (EAS) AF: 0.276 AC: 1427 AN: 5164

South Asian (SAS) AF: 0.174 AC: 834 AN: 4804

European-Finnish (FIN) AF: 0.201 AC: 2129 AN: 10568

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9084 AN: 67966

Other (OTH) AF: 0.142 AC: 299 AN: 2108

Alfa AF: 0.142 Hom.: 6481

Bravo AF: 0.161

Asia WGS AF: 0.207 AC: 720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.54
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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