ENST00000679386.1:c.1758+7368G>A

Variant names:

• chr21-41460237-G-A
• rs8127290
• ENST00000679386.1:c.1758+7368G>A

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 5 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]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

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

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		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

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	Intron 16 of 16	Prot: ENSP00000505700.1 UniProt:

MX1 ENST00000679386.1

HGVSc / HGVSpc.1758+7368G>A

Exon rankIntron 16 of 16

intron

Prot: ENSP00000505700.1UniProt: A0A7P0T9R0

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.220	AC:33391	Hom:4360	AN:151898	Cov:32
GnomAD4 genome	AF: 0.220	AC:33445	Hom:4371	AN:152016	Cov:32
TOPMed (Bravo)	AF: 0.214	AC:56723	Hom:7316	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.184	AC:15348	Hom:1583	AN:83522	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.170	AC:399	Hom:37	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.278	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.143	AC:43	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.303	AC:1058	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.229	AC:1653	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.165	AC:29	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.246	AC:30198	Hom:3703	AN:122732	Cov:
Turkish Variome	AF: 0.145	AC:224	Hom:16	AN:1546	Cov:
UK10K	AF: 0.155	AC:1173	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.299	AC:2682	Hom:425	AN:8960	Cov:

Showing 14 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.33
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.25
DANN	Benign	0.73
GPN-Star LLR	N/A	0.090
GPN-Star score	N/A	-0.090
PhyloP100	Benign	-1.2

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0

Showing 1 of 1 scores

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.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs8127290;

hg19: chr21-42832164;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar