rs462903

Positions:

• chr21-41425679-G-A
• chr21-41425679-G-T
• chr21-41425679-G-C

Variant summary

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

The NM_001144925.2(MX1):​c.-308-1527G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 152,014 control chromosomes in the GnomAD database, including 37,980 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 0.69 (37980 hom., cov: 31)
• Consequence: MX1 NM_001144925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MX1	NM_001144925.2	c.-308-1527G>A		intron_variant
MX1	XM_011529568.3	c.-308-1527G>A		intron_variant
MX1	XM_017028349.3	c.-327-1527G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MX1	ENST00000398600.6	c.-308-1527G>A		intron_variant		2		P1
MX1	ENST00000413778.6	c.-327-1527G>A		intron_variant		5		P1
MX1	ENST00000679445.1	c.-308-1527G>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105095 AN: 151896 Hom.: 37924 Cov.: 31

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.695

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

GnomAD4 genome AF: 0.692 AC: 105213 AN: 152014 Hom.: 37980 Cov.: 31 AF XY: 0.695 AC XY: 51642 AN XY: 74298

Gnomad4 AFR AF: 0.854

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.705

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.696

Alfa AF: 0.622 Hom.: 11610

Bravo AF: 0.712

Asia WGS AF: 0.885 AC: 3074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.1
DANN	Benign	0.64

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

LitVar

Other links and lift over

dbSNP: rs462903; hg19: chr21-42797606;