rs2838035

Positions:

• chr21-41428539-T-G
• chr21-41428539-T-A

Variant summary

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

The NM_002462.5(MX1):​c.-98+673T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,280 control chromosomes in the GnomAD database, including 1,602 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 0.14 (1602 hom., cov: 33)
  • Exomes 𝑓: 0.16 (0 hom.)
• Consequence: MX1 NM_002462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01

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 (SAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MX1	NM_002462.5	c.-98+673T>G		intron_variant		ENST00000398598.8	NP_002453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MX1	ENST00000398598.8	c.-98+673T>G		intron_variant		1	NM_002462.5	ENSP00000381599	P1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21497 AN: 152130 Hom.: 1601 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0954

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.156 AC: 5 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 4 AN XY: 24

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.154

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.141 AC: 21510 AN: 152248 Hom.: 1602 Cov.: 33 AF XY: 0.142 AC XY: 10561 AN XY: 74446

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.0954

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.127

Alfa AF: 0.111 Hom.: 278

Bravo AF: 0.142

Asia WGS AF: 0.169 AC: 591 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	1.7
DANN	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2838035; hg19: chr21-42800466;