Genetic Variant NM_002462.5:c.-97-893C>G (chr21-41429640-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.-97-893C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 151,984 control chromosomes in the GnomAD database, including 5,736 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 0.26 ( 5736 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

MX1
NM_002462.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0490

Publications

6 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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.402 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
MX1	NM_002462.5	MANE Select	c.-97-893C>G	intron	N/A	NP_002453.2
MX1	NM_001144925.2		c.-97-893C>G	intron	N/A	NP_001138397.1
MX1	NM_001178046.3		c.-22+1774C>G	intron	N/A	NP_001171517.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MX1	ENST00000398598.8	TSL:1 MANE Select	c.-97-893C>G	intron	N/A	ENSP00000381599.3
MX1	ENST00000455164.6	TSL:1	c.-22+1774C>G	intron	N/A	ENSP00000410523.2
MX1	ENST00000478268.1	TSL:2	n.2921C>G	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38926

AN:

151862

Hom.:

5712

Cov.:

show subpopulations

Gnomad AFR

AF:

0.373

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.417

Gnomad SAS

AF:

0.392

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.238

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.257

AC:

39003

AN:

151980

Hom.:

5736

Cov.:

AF XY:

0.258

AC XY:

19186

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.374

AC:

15486

AN:

41412

American (AMR)

AF:

0.293

AC:

4475

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

547

AN:

3472

East Asian (EAS)

AF:

0.417

AC:

2146

AN:

5152

South Asian (SAS)

AF:

0.392

AC:

1881

AN:

4800

European-Finnish (FIN)

AF:

0.172

AC:

1826

AN:

10586

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.175

AC:

11899

AN:

67968

Other (OTH)

AF:

0.237

AC:

500

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1420

2840

4260

5680

7100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.218

Hom.:

499

Bravo

AF:

0.269

Asia WGS

AF:

0.388

AC:

1351

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.8

(source)

DANN

Benign

0.57

PhyloP100

-0.049

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over