rs17000900

Positions:

• chr21-41426103-C-A
• chr21-41426103-C-T

Variant summary

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

The ENST00000455164(MX1):​c.-294C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 173,842 control chromosomes in the GnomAD database, including 1,764 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 (1671 hom., cov: 33)
  • Exomes 𝑓: 0.089 (93 hom.)
• Consequence: MX1 ENST00000455164 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138

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]

MX1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MX1	NM_001144925.2	c.-308-1103C>A		intron_variant			NP_001138397.1
MX1	XM_011529568.3	c.-308-1103C>A		intron_variant			XP_011527870.1
MX1	XM_017028349.3	c.-327-1103C>A		intron_variant			XP_016883838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MX1	ENST00000455164	c.-294C>A		5_prime_UTR_variant	1/15	1		ENSP00000410523.2
MX1	ENST00000419044	c.-367C>A		5_prime_UTR_variant	1/17	3		ENSP00000392151.2
MX1	ENST00000679705	c.-386C>A		5_prime_UTR_variant	1/17			ENSP00000506372.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20871 AN: 152184 Hom.: 1672 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0838

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.0820

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.0889 AC: 1914 AN: 21540 Hom.: 93 Cov.: 0 AF XY: 0.0882 AC XY: 1002 AN XY: 11360

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.0977

Gnomad4 ASJ exome AF: 0.0598

Gnomad4 EAS exome AF: 0.149

Gnomad4 SAS exome AF: 0.193

Gnomad4 FIN exome AF: 0.0741

Gnomad4 NFE exome AF: 0.0797

Gnomad4 OTH exome AF: 0.0796

GnomAD4 genome AF: 0.137 AC: 20889 AN: 152302 Hom.: 1671 Cov.: 33 AF XY: 0.135 AC XY: 10067 AN XY: 74476

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0838

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.0820

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.121

Alfa AF: 0.0765 Hom.: 126

Bravo AF: 0.141

Asia WGS AF: 0.159 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.7
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17000900; hg19: chr21-42798030;