dbSNP rs35870315: MX1:c.1009-21T>C (chr21-41445427-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.138

Publications

4 publications found

Variant links:

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 links:

MX1-AS1 (HGNC:40383):

MX1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MX1	NM_002462.5 link	c.1009-21T>C		intron_variant	Intron 11 of 16	ENST00000398598.8	NP_002453.2	P20591-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MX1	ENST00000398598.8 link	c.1009-21T>C		intron_variant	Intron 11 of 16	1	NM_002462.5	ENSP00000381599.3		P20591-1

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16449

AN:

152090

Hom.:

1012

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.109

AC XY:

79326

AN XY:

726544

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

6812

13625

20437

27250

34062

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4026

8052

12078

16104

20130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.108

AC:

16453

AN:

152208

Hom.:

1011

Cov.:

AF XY:

0.112

AC XY:

8361

AN XY:

74438

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.103

AC:

7025

AN:

68006

Other (OTH)

AF:

0.0914

AC:

193

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

760

1521

2281

3042

3802

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

9.2

(source)

DANN

Benign

0.84

PhyloP100

0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over