rs8127664

Positions:

• chr21-41460711-C-T
• chr21-41460711-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000679386.1(MX1):​c.1759-7526C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,034 control chromosomes in the GnomAD database, including 2,889 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 0.18 (2889 hom., cov: 31)
• Consequence: MX1 ENST00000679386.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MX1	ENST00000679386.1	c.1759-7526C>T		intron_variant				ENSP00000505700

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27718 AN: 151916 Hom.: 2882 Cov.: 31

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0871

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.183 AC: 27759 AN: 152034 Hom.: 2889 Cov.: 31 AF XY: 0.188 AC XY: 13969 AN XY: 74288

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0871

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.146

Alfa AF: 0.155 Hom.: 3820

Bravo AF: 0.173

Asia WGS AF: 0.274 AC: 953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.55
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8127664; hg19: chr21-42832638;