rs35870315

Variant names:

• chr21-41445427-T-C
• rs35870315
• NM_002462.5:c.1009-21T>C

Variant summary

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

The NM_002462.5(MX1):​c.1009-21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,612,552 control chromosomes in the GnomAD database, including 10,601 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 0.11 (1011 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9590 hom.)
• Consequence: MX1 NM_002462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• Publications: 4 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002462.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MX1	NM_002462.5	MANE Select	c.1009-21T>C		intron	N/A	NP_002453.2	P20591-1
	MX1	NM_001144925.2		c.1009-21T>C		intron	N/A	NP_001138397.1	P20591-1
	MX1	NM_001178046.3		c.1009-21T>C		intron	N/A	NP_001171517.1	P20591-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MX1	ENST00000398598.8	TSL:1 MANE Select	c.1009-21T>C		intron	N/A	ENSP00000381599.3	P20591-1
	MX1	ENST00000455164.6	TSL:1	c.1009-21T>C		intron	N/A	ENSP00000410523.2	P20591-1
	MX1	ENST00000896042.1		c.1009-21T>C		intron	N/A	ENSP00000566101.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16449 AN: 152090 Hom.: 1012 Cov.: 32

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0737

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0919

GnomAD2 exomes AF: 0.130 AC: 32663 AN: 250534 AF XY: 0.128

Gnomad AFR exome AF: 0.0847

Gnomad AMR exome AF: 0.213

Gnomad ASJ exome AF: 0.0727

Gnomad EAS exome AF: 0.158

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.101

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.108 AC: 157866 AN: 1460344 Hom.: 9590 Cov.: 32 AF XY: 0.109 AC XY: 79326 AN XY: 726544

African (AFR) AF: 0.0855 AC: 2854 AN: 33364

American (AMR) AF: 0.204 AC: 9105 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.0762 AC: 1990 AN: 26108

East Asian (EAS) AF: 0.191 AC: 7586 AN: 39688

South Asian (SAS) AF: 0.154 AC: 13279 AN: 86198

European-Finnish (FIN) AF: 0.154 AC: 8223 AN: 53324

Middle Eastern (MID) AF: 0.0786 AC: 453 AN: 5760

European-Non Finnish (NFE) AF: 0.0972 AC: 108031 AN: 1111018

Other (OTH) AF: 0.105 AC: 6345 AN: 60312

GnomAD4 genome AF: 0.108 AC: 16453 AN: 152208 Hom.: 1011 Cov.: 32 AF XY: 0.112 AC XY: 8361 AN XY: 74438

African (AFR) AF: 0.0887 AC: 3684 AN: 41512

American (AMR) AF: 0.121 AC: 1852 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0737 AC: 256 AN: 3472

East Asian (EAS) AF: 0.166 AC: 860 AN: 5176

South Asian (SAS) AF: 0.149 AC: 719 AN: 4822

European-Finnish (FIN) AF: 0.164 AC: 1741 AN: 10604

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7025 AN: 68006

Other (OTH) AF: 0.0914 AC: 193 AN: 2112

Alfa AF: 0.108 Hom.: 288

Bravo AF: 0.104

Asia WGS AF: 0.137 AC: 479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.2
DANN	Benign	0.84
PhyloP100		0.14
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: rs35870315; hg19: chr21-42817354; COSMIC: COSV55819397; COSMIC: COSV55819397;