20-32358849-A-AG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_015338.6(ASXL1):c.57+23dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000096 in 1,270,438 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000061 (0 hom.)
• Consequence: ASXL1 NM_015338.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0760

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 20-32358849-A-AG is Benign according to our data. Variant chr20-32358849-A-AG is described in ClinVar as [Benign]. Clinvar id is 1901363.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 54 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASXL1	NM_015338.6	c.57+23dup		intron_variant		ENST00000375687.10
ASXL1	NM_001164603.1	c.57+23dup		intron_variant
ASXL1	XM_006723727.4	c.57+23dup		intron_variant
ASXL1	XM_047439945.1	c.57+23dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASXL1	ENST00000375687.10	c.57+23dup		intron_variant		5	NM_015338.6	P1

Frequencies

GnomAD3 genomes AF: 0.000362 AC: 54 AN: 149304 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000265

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000201

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000683 AC: 7 AN: 102422 Hom.: 0 AF XY: 0.0000528 AC XY: 3 AN XY: 56796

Gnomad AFR exome AF: 0.000656

Gnomad AMR exome AF: 0.000215

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000181

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000293

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000607 AC: 68 AN: 1121020 Hom.: 0 Cov.: 33 AF XY: 0.0000590 AC XY: 33 AN XY: 559552

Gnomad4 AFR exome AF: 0.00173

Gnomad4 AMR exome AF: 0.000133

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000345

Gnomad4 SAS exome AF: 0.0000429

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000188

Gnomad4 OTH exome AF: 0.000106

GnomAD4 genome AF: 0.000361 AC: 54 AN: 149418 Hom.: 0 Cov.: 31 AF XY: 0.000329 AC XY: 24 AN XY: 72962

Gnomad4 AFR AF: 0.00121

Gnomad4 AMR AF: 0.000264

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000202

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000141 Hom.: 0

Bravo AF: 0.000378

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 13, 2023

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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: rs757765039; hg19: chr20-30946652;