rs17000900

Variant names:

• chr21-41426103-C-A
• rs17000900
• ENST00000455164.6:c.-294C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000455164.6(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 ENST00000455164.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138
• Publications: 29 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000455164.6. 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
	MX1	NM_001144925.2		c.-308-1103C>A		intron	N/A	NP_001138397.1	P20591-1
	MX1	NM_002462.5	MANE Select	c.-469C>A		upstream_gene	N/A	NP_002453.2	P20591-1
	MX1	NM_001178046.3		c.-294C>A		upstream_gene	N/A	NP_001171517.1	P20591-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MX1	ENST00000455164.6	TSL:1	c.-294C>A		5_prime_UTR	Exon 1 of 15	ENSP00000410523.2	P20591-1
	MX1	ENST00000915292.1		c.-311C>A		splice_region	Exon 1 of 17	ENSP00000585351.1
	MX1	ENST00000419044.6	TSL:3	c.-367C>A		5_prime_UTR	Exon 1 of 17	ENSP00000392151.2	P20591-1

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

African (AFR) AF: 0.151 AC: 80 AN: 530

American (AMR) AF: 0.0977 AC: 43 AN: 440

Ashkenazi Jewish (ASJ) AF: 0.0598 AC: 36 AN: 602

East Asian (EAS) AF: 0.149 AC: 342 AN: 2300

South Asian (SAS) AF: 0.193 AC: 29 AN: 150

European-Finnish (FIN) AF: 0.0741 AC: 194 AN: 2618

Middle Eastern (MID) AF: 0.105 AC: 9 AN: 86

European-Non Finnish (NFE) AF: 0.0797 AC: 1086 AN: 13620

Other (OTH) AF: 0.0796 AC: 95 AN: 1194

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

African (AFR) AF: 0.206 AC: 8548 AN: 41550

American (AMR) AF: 0.109 AC: 1669 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0838 AC: 291 AN: 3472

East Asian (EAS) AF: 0.149 AC: 772 AN: 5180

South Asian (SAS) AF: 0.228 AC: 1100 AN: 4824

European-Finnish (FIN) AF: 0.0820 AC: 871 AN: 10622

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7194 AN: 68032

Other (OTH) AF: 0.121 AC: 255 AN: 2114

Alfa AF: 0.116 Hom.: 381

Bravo AF: 0.141

Asia WGS AF: 0.159 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.7
DANN	Benign	0.59
PhyloP100		-0.14
PromoterAI		0.27	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs17000900;

hg19: chr21-42798030;