rs1250550

Positions:

• chr10-79300560-C-A
• chr10-79300560-C-G

Variant summary

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

The NM_020338.4(ZMIZ1):​c.1809-172C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 150,622 control chromosomes in the GnomAD database, including 6,531 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 0.27 (6531 hom., cov: 30)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358

Genes affected

ZMIZ1 (HGNC:16493): (zinc finger MIZ-type containing 1) This gene encodes a member of the PIAS (protein inhibitor of activated STAT) family of proteins. The encoded protein regulates the activity of various transcription factors, including the androgen receptor, Smad3/4, and p53. The encoded protein may also play a role in sumoylation. A translocation between this locus on chromosome 10 and the protein tyrosine kinase ABL1 locus on chromosome 9 has been associated with acute lymphoblastic leukemia. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMIZ1	NM_020338.4	c.1809-172C>A		intron_variant		ENST00000334512.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMIZ1	ENST00000334512.10	c.1809-172C>A		intron_variant		5	NM_020338.4	P1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41112 AN: 150506 Hom.: 6527 Cov.: 30

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.234

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.273 AC: 41122 AN: 150622 Hom.: 6531 Cov.: 30 AF XY: 0.277 AC XY: 20370 AN XY: 73416

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.233

Alfa AF: 0.316 Hom.: 6055

Bravo AF: 0.251

Asia WGS AF: 0.306 AC: 1062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.59

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: rs1250550; hg19: chr10-81060317; COSMIC: COSV57898137; COSMIC: COSV57898137;