rs469083

Variant names:

• chr21-41436789-C-T
• rs469083
• NM_002462.5:c.299-226C>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.299-226C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,002 control chromosomes in the GnomAD database, including 27,924 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 0.60 (27924 hom., cov: 32)
• Consequence: MX1 NM_002462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MX1	NM_002462.5	c.299-226C>T		intron_variant	Intron 6 of 16	ENST00000398598.8	NP_002453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MX1	ENST00000398598.8	c.299-226C>T		intron_variant	Intron 6 of 16	1	NM_002462.5	ENSP00000381599.3

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91177 AN: 151884 Hom.: 27891 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.600 AC: 91274 AN: 152002 Hom.: 27924 Cov.: 32 AF XY: 0.596 AC XY: 44266 AN XY: 74278

African (AFR) AF: 0.539 AC: 22339 AN: 41432

American (AMR) AF: 0.593 AC: 9059 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1641 AN: 3466

East Asian (EAS) AF: 0.281 AC: 1456 AN: 5176

South Asian (SAS) AF: 0.515 AC: 2480 AN: 4820

European-Finnish (FIN) AF: 0.645 AC: 6808 AN: 10562

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.668 AC: 45409 AN: 67952

Other (OTH) AF: 0.584 AC: 1233 AN: 2112

Alfa AF: 0.639 Hom.: 22633

Bravo AF: 0.592

Asia WGS AF: 0.383 AC: 1336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.52
PhyloP100		0.34
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: rs469083; hg19: chr21-42808716;