rs469270

Variant names:

• chr21-41445250-G-A
• rs469270
• NM_002462.5:c.1009-198G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002462.5(MX1):​c.1009-198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,842 control chromosomes in the GnomAD database, including 19,616 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 0.50 (19616 hom., cov: 30)
• Consequence: MX1 NM_002462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199
• Publications: 2 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]

MX1-AS1 (HGNC:40383):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MX1	NM_002462.5	c.1009-198G>A		intron_variant	Intron 11 of 16	ENST00000398598.8	NP_002453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MX1	ENST00000398598.8	c.1009-198G>A		intron_variant	Intron 11 of 16	1	NM_002462.5	ENSP00000381599.3

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75148 AN: 151724 Hom.: 19608 Cov.: 30

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.495 AC: 75200 AN: 151842 Hom.: 19616 Cov.: 30 AF XY: 0.486 AC XY: 36089 AN XY: 74222

African (AFR) AF: 0.407 AC: 16856 AN: 41380

American (AMR) AF: 0.476 AC: 7267 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1589 AN: 3468

East Asian (EAS) AF: 0.103 AC: 531 AN: 5148

South Asian (SAS) AF: 0.371 AC: 1787 AN: 4816

European-Finnish (FIN) AF: 0.503 AC: 5309 AN: 10558

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40045 AN: 67892

Other (OTH) AF: 0.499 AC: 1050 AN: 2106

Alfa AF: 0.527 Hom.: 2836

Bravo AF: 0.487

Asia WGS AF: 0.238 AC: 829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.9
DANN	Benign	0.86
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs469270; hg19: chr21-42817177;