rs464397

Variant names:

• chr21-41428591-T-C
• rs464397
• NM_002462.5:c.-98+725T>C

Your query was ambiguous. Multiple possible variants found:

• chr21-41428591-T-C
• chr21-41428591-T-G

Variant summary

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

The NM_002462.5(MX1):​c.-98+725T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,170 control chromosomes in the GnomAD database, including 33,084 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 0.64 (33082 hom., cov: 32)
  • Exomes 𝑓: 0.44 (2 hom.)
• Consequence: MX1 NM_002462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928
• Publications: 22 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MX1	NM_002462.5	c.-98+725T>C		intron_variant	Intron 3 of 16	ENST00000398598.8	NP_002453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MX1	ENST00000398598.8	c.-98+725T>C		intron_variant	Intron 3 of 16	1	NM_002462.5	ENSP00000381599.3

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97182 AN: 152034 Hom.: 33032 Cov.: 32

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.628

GnomAD4 exome AF: 0.444 AC: 8 AN: 18 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 5 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.375 AC: 3 AN: 8

Other (OTH) AF: 0.500 AC: 3 AN: 6

GnomAD4 genome AF: 0.639 AC: 97294 AN: 152152 Hom.: 33082 Cov.: 32 AF XY: 0.644 AC XY: 47860 AN XY: 74370

African (AFR) AF: 0.829 AC: 34436 AN: 41522

American (AMR) AF: 0.691 AC: 10571 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 2312 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5128 AN: 5162

South Asian (SAS) AF: 0.734 AC: 3539 AN: 4824

European-Finnish (FIN) AF: 0.520 AC: 5498 AN: 10582

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33882 AN: 67978

Other (OTH) AF: 0.630 AC: 1332 AN: 2114

Alfa AF: 0.617 Hom.: 5587

Bravo AF: 0.661

Asia WGS AF: 0.859 AC: 2985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.36
PhyloP100		-0.93
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: rs464397; hg19: chr21-42800518;