Genetic Variant NM_002462.5:c.-98+397C>G (chr21-41428263-C-G) – 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.-98+397C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,216 control chromosomes in the GnomAD database, including 7,949 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 0.31 ( 7948 hom., cov: 33)

Exomes 𝑓: 0.39 ( 1 hom. )

Consequence

MX1
NM_002462.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.212

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:

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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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MX1	NM_002462.5	MANE Select	c.-98+397C>G	intron	N/A	NP_002453.2	P20591-1
MX1	NM_001144925.2		c.-98+397C>G	intron	N/A	NP_001138397.1	P20591-1
MX1	NM_001178046.3		c.-22+397C>G	intron	N/A	NP_001171517.1	P20591-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MX1	ENST00000398598.8	TSL:1 MANE Select	c.-98+397C>G	intron	N/A	ENSP00000381599.3	P20591-1
MX1	ENST00000455164.6	TSL:1	c.-22+397C>G	intron	N/A	ENSP00000410523.2	P20591-1
MX1	ENST00000896042.1		c.-98+397C>G	intron	N/A	ENSP00000566101.1

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

47933

AN:

152080

Hom.:

7952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.240

Gnomad AMR

AF:

0.366

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.570

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.347

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.321

Gnomad OTH

AF:

0.342

GnomAD4 exome

AF:

0.389

AC:

AN:

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.286

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.315

AC:

47926

AN:

152198

Hom.:

7948

Cov.:

AF XY:

0.318

AC XY:

23694

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.228

AC:

9458

AN:

41546

American (AMR)

AF:

0.365

AC:

5582

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.505

AC:

1751

AN:

3468

East Asian (EAS)

AF:

0.571

AC:

2957

AN:

5182

South Asian (SAS)

AF:

0.335

AC:

1614

AN:

4824

European-Finnish (FIN)

AF:

0.347

AC:

3667

AN:

10576

Middle Eastern (MID)

AF:

0.432

AC:

126

AN:

292

European-Non Finnish (NFE)

AF:

0.321

AC:

21826

AN:

67996

Other (OTH)

AF:

0.344

AC:

727

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1708

3416

5125

6833

8541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.160

Hom.:

297

Bravo

AF:

0.315

Asia WGS

AF:

0.441

AC:

1528

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.8

(source)

DANN

Benign

0.41

PhyloP100

0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over