chr21-41432752-G-A

Variant names:

• chr21-41432752-G-A
• rs455599
• NM_002462.5:c.105+577G>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.105+577G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,102 control chromosomes in the GnomAD database, including 33,657 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 (33657 hom., cov: 32)
• Consequence: MX1 NM_002462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MX1	NM_002462.5	c.105+577G>A		intron_variant	Intron 5 of 16	ENST00000398598.8	NP_002453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MX1	ENST00000398598.8	c.105+577G>A		intron_variant	Intron 5 of 16	1	NM_002462.5	ENSP00000381599.3

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97791 AN: 151984 Hom.: 33615 Cov.: 32

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.644 AC: 97894 AN: 152102 Hom.: 33657 Cov.: 32 AF XY: 0.648 AC XY: 48164 AN XY: 74356

African (AFR) AF: 0.848 AC: 35215 AN: 41504

American (AMR) AF: 0.699 AC: 10677 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2320 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5147 AN: 5184

South Asian (SAS) AF: 0.734 AC: 3539 AN: 4822

European-Finnish (FIN) AF: 0.519 AC: 5482 AN: 10558

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33573 AN: 67968

Other (OTH) AF: 0.636 AC: 1343 AN: 2112

Alfa AF: 0.574 Hom.: 3497

Bravo AF: 0.668

Asia WGS AF: 0.845 AC: 2937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.4
DANN	Benign	0.76
PhyloP100		-0.23
Mutation Taster		=99/1	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: rs455599; hg19: chr21-42804679;