rs461093

Positions:

• chr21-41428263-C-G
• chr21-41428263-C-T

Variant summary

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

The NM_002462.5(MX1):​c.-98+397C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,216 control chromosomes in the GnomAD database, including 7,949 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 0.31 (7948 hom., cov: 33)
  • Exomes 𝑓: 0.39 (1 hom.)
• Consequence: MX1 NM_002462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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 = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MX1	NM_002462.5	c.-98+397C>G		intron_variant		ENST00000398598.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MX1	ENST00000398598.8	c.-98+397C>G		intron_variant		1	NM_002462.5	P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47933 AN: 152080 Hom.: 7952 Cov.: 33

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.342

GnomAD4 exome AF: 0.389 AC: 7 AN: 18 Hom.: 1 Cov.: 0 AF XY: 0.333 AC XY: 4 AN XY: 12

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.286

GnomAD4 genome AF: 0.315 AC: 47926 AN: 152198 Hom.: 7948 Cov.: 33 AF XY: 0.318 AC XY: 23694 AN XY: 74396

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.344

Alfa AF: 0.160 Hom.: 297

Bravo AF: 0.315

Asia WGS AF: 0.441 AC: 1528 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	3.8
DANN	Benign	0.41

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: rs461093; hg19: chr21-42800190;