dbSNP rs8127290: MX1:c.1758+7368G>A (chr21-41460237-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The ENST00000679386.1(MX1):c.1758+7368G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: ENST00000679386.1 is not a MANE Select or MANE Plus Clinical transcript for MX1; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.22 (AC=33,445) in the gnomAD database across 152,016 control chromosomes, including 4,371 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.34. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 4371 hom., cov: 32)

Consequence

MX1
ENST00000679386.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.18

Publications

5 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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new If you want to explore the variant's impact on the transcript ENST00000679386.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.3398 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000679386.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MX1	ENST00000679386.1		c.1758+7368G>A		intron	N/A	ENSP00000505700.1	A0A7P0T9R0

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33391

AN:

151898

Hom.:

4360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.344

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.0957

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.224

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.140

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.177

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.220

AC:

33445

AN:

152016

Hom.:

4371

Cov.:

AF XY:

0.224

AC XY:

16650

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.345

AC:

14267

AN:

41412

American (AMR)

AF:

0.128

AC:

1959

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0957

AC:

332

AN:

3468

East Asian (EAS)

AF:

0.292

AC:

1510

AN:

5166

South Asian (SAS)

AF:

0.223

AC:

1072

AN:

4816

European-Finnish (FIN)

AF:

0.265

AC:

2801

AN:

10566

Middle Eastern (MID)

AF:

0.144

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.160

AC:

10898

AN:

67974

Other (OTH)

AF:

0.178

AC:

376

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1277

2554

3830

5107

6384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

TOPMed (Bravo)

AF:

0.214

AC:

56723

AN:

264690

Hom.:

7316

ALFA (dbGaP/dbSNP Allele Frequency Aggregator)

AF:

0.184

AC:

15348

AN:

83522

Hom.:

1583

Local populations

ABraOM SABE-WGS-1171

AF:

0.170

AC:

399

AN:

2342

Hom.:

ChinaMAP Phase 1

AF:

0.278

Denmark Genome

AF:

0.143

AC:

AN:

300

GenomeAsia100K

AF:

0.303

AC:

1058

AN:

3478

show subpopulations

Oceania

AF:

0.669

AC:

AN:

148

Hom.:

North-East Asia

AF:

0.202

AC:

142

AN:

702

Hom.:

South-East Asia

AF:

0.429

AC:

297

AN:

692

Hom.:

South Asia

AF:

0.278

AC:

403

AN:

1448

Hom.:

Africa

AF:

0.365

AC:

AN:

208

Hom.:

America

AF:

0.115

AC:

AN:

Hom.:

West Eurasia

AF:

0.154

AC:

AN:

228

Hom.:

Korea4K (4,157 Koreans)

AF:

0.229

AC:

1653

AN:

7234

Qatari Genome

AF:

0.165

AC:

AN:

176

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.246

AC:

30198

AN:

122732

Hom.:

3703

Turkish Variome

AF:

0.145

AC:

224

AN:

1546

Hom.:

UK10K

AF:

0.155

AC:

1173

AN:

7562

show subpopulations

TwinsUK

AF:

0.155

AC:

553

AN:

3574

ALSPAC

AF:

0.156

AC:

602

AN:

3854

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.299

AC:

2682

AN:

8960

Hom.:

425

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.25

(source)

DANN

Benign

0.73

PhyloP100

-1.2

AlphaGenome AVI

Benign

0.33

(source)

GPN-Star LLR

0.090

(source)

GPN-Star score

-0.090

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Pangolin (max)

Benign

0.0

(source)

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over