20-32359043-G-GC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015338.6(ASXL1):c.57+219dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00934 in 597,594 control chromosomes in the GnomAD database, including 183 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (65 hom., cov: 31)
  • Exomes 𝑓: 0.0081 (118 hom.)
• Consequence: ASXL1 NM_015338.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.273

Genes affected

ASXL1 (HGNC:18318): (ASXL transcriptional regulator 1) This gene is similar to the Drosophila additional sex combs gene, which encodes a chromatin-binding protein required for normal determination of segment identity in the developing embryo. The protein is a member of the Polycomb group of proteins, which are necessary for the maintenance of stable repression of homeotic and other loci. The protein is thought to disrupt chromatin in localized areas, enhancing transcription of certain genes while repressing the transcription of other genes. The protein encoded by this gene functions as a ligand-dependent co-activator for retinoic acid receptor in cooperation with nuclear receptor coactivator 1. Mutations in this gene are associated with myelodysplastic syndromes and chronic myelomonocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 20-32359043-G-GC is Benign according to our data. Variant chr20-32359043-G-GC is described in ClinVar as [Likely_benign]. Clinvar id is 1182355.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASXL1	NM_015338.6	c.57+219dup		intron_variant		ENST00000375687.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASXL1	ENST00000375687.10	c.57+219dup		intron_variant		5	NM_015338.6	P1

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1975 AN: 150570 Hom.: 66 Cov.: 31

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0732

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.0109

Gnomad SAS AF: 0.00422

Gnomad FIN AF: 0.0000961

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.000963

Gnomad OTH AF: 0.0117

GnomAD4 exome AF: 0.00807 AC: 3608 AN: 446910 Hom.: 118 Cov.: 5 AF XY: 0.00755 AC XY: 1776 AN XY: 235284

Gnomad4 AFR exome AF: 0.0164

Gnomad4 AMR exome AF: 0.0946

Gnomad4 ASJ exome AF: 0.000378

Gnomad4 EAS exome AF: 0.0330

Gnomad4 SAS exome AF: 0.00384

Gnomad4 FIN exome AF: 0.000370

Gnomad4 NFE exome AF: 0.00149

Gnomad4 OTH exome AF: 0.00813

GnomAD4 genome AF: 0.0131 AC: 1976 AN: 150684 Hom.: 65 Cov.: 31 AF XY: 0.0138 AC XY: 1016 AN XY: 73628

Gnomad4 AFR AF: 0.0170

Gnomad4 AMR AF: 0.0733

Gnomad4 ASJ AF: 0.000290

Gnomad4 EAS AF: 0.0109

Gnomad4 SAS AF: 0.00401

Gnomad4 FIN AF: 0.0000961

Gnomad4 NFE AF: 0.000963

Gnomad4 OTH AF: 0.0115

Bravo AF: 0.0195

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs545230525; hg19: chr20-30946846;