21-41432752-G-A

Position:

• chr21-41432752-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MX1	NM_002462.5	c.105+577G>A		intron_variant		ENST00000398598.8	NP_002453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MX1	ENST00000398598.8	c.105+577G>A		intron_variant		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

Gnomad4 AFR AF: 0.848

Gnomad4 AMR AF: 0.699

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.734

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.636

Alfa AF: 0.563 Hom.: 3221

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs455599; hg19: chr21-42804679;