chr21-41445427-T-C

Position:

• chr21-41445427-T-C

Variant summary

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

The NM_002462.5(MX1):​c.1009-21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,612,552 control chromosomes in the GnomAD database, including 10,601 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 0.11 (1011 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9590 hom.)
• Consequence: MX1 NM_002462.5 intron
• 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]

(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 (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MX1	NM_002462.5	c.1009-21T>C		intron_variant		ENST00000398598.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MX1	ENST00000398598.8	c.1009-21T>C		intron_variant		1	NM_002462.5	P1
	ENST00000411427.3	n.219+63A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16449 AN: 152090 Hom.: 1012 Cov.: 32

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0737

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0919

GnomAD3 exomes AF: 0.130 AC: 32663 AN: 250534 Hom.: 2485 AF XY: 0.128 AC XY: 17356 AN XY: 135508

Gnomad AFR exome AF: 0.0847

Gnomad AMR exome AF: 0.213

Gnomad ASJ exome AF: 0.0727

Gnomad EAS exome AF: 0.158

Gnomad SAS exome AF: 0.155

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.101

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.108 AC: 157866 AN: 1460344 Hom.: 9590 Cov.: 32 AF XY: 0.109 AC XY: 79326 AN XY: 726544

Gnomad4 AFR exome AF: 0.0855

Gnomad4 AMR exome AF: 0.204

Gnomad4 ASJ exome AF: 0.0762

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.154

Gnomad4 NFE exome AF: 0.0972

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.108 AC: 16453 AN: 152208 Hom.: 1011 Cov.: 32 AF XY: 0.112 AC XY: 8361 AN XY: 74438

Gnomad4 AFR AF: 0.0887

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.0737

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0914

Alfa AF: 0.109 Hom.: 282

Bravo AF: 0.104

Asia WGS AF: 0.137 AC: 479 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	9.2
DANN	Benign	0.84

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: rs35870315; hg19: chr21-42817354; COSMIC: COSV55819397; COSMIC: COSV55819397;