21-41460711-C-T

Variant names:

• chr21-41460711-C-T
• rs8127664
• ENST00000679386.1:c.1759-7526C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000679386.1. You can select a different transcript below to see updated ACMG 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.1759-7526C>T		intron	N/A	ENSP00000505700.1	A0A7P0T9R0

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

African (AFR) AF: 0.230 AC: 9544 AN: 41450

American (AMR) AF: 0.107 AC: 1643 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0871 AC: 302 AN: 3468

East Asian (EAS) AF: 0.292 AC: 1504 AN: 5148

South Asian (SAS) AF: 0.203 AC: 980 AN: 4816

European-Finnish (FIN) AF: 0.264 AC: 2789 AN: 10572

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10482 AN: 67974

Other (OTH) AF: 0.146 AC: 307 AN: 2104

Alfa AF: 0.160 Hom.: 5992

Bravo AF: 0.173

Asia WGS AF: 0.274 AC: 953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.55
DANN	Benign	0.55
PhyloP100		-1.5

Splicing

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.

Other links and lift over

dbSNP: rs8127664;

hg19: chr21-42832638;