rs886056593

Variant names:

• chr20-32358685-ACCG-A
• rs886056593
• NM_015338.6:c.-79_-77delGCC

Your query was ambiguous. Multiple possible variants found:

• chr20-32358685-ACCG-A
• chr20-32358685-ACCG-ACCGCCG
• chr20-32358685-ACCG-ACCGCCGCCG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015338.6(ASXL1):​c.-79_-77delGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000727 in 371,410 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000073 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ASXL1 NM_015338.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151
• Publications: 0 publications found

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]

ASXL1 Gene-Disease associations (from GenCC):

• Bohring-Opitz syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, Laboratory for Molecular Medicine, Orphanet, G2P, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015338.6. 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
	ASXL1	NM_015338.6	MANE Select	c.-79_-77delGCC		5_prime_UTR	Exon 1 of 13	NP_056153.2
	ASXL1	NM_001164603.1		c.-79_-77delGCC		5_prime_UTR	Exon 1 of 5	NP_001158075.1	Q498B9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASXL1	ENST00000375687.10	TSL:5 MANE Select	c.-79_-77delGCC		5_prime_UTR	Exon 1 of 13	ENSP00000364839.4	Q8IXJ9-1
	ASXL1	ENST00000905973.1		c.-79_-77delGCC		5_prime_UTR	Exon 1 of 12	ENSP00000576032.1
	ASXL1	ENST00000915088.1		c.-79_-77delGCC		5_prime_UTR	Exon 1 of 11	ENSP00000585147.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 129906 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD4 exome AF: 0.0000727 AC: 27 AN: 371410 Hom.: 0 AF XY: 0.0000947 AC XY: 17 AN XY: 179548

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 6768

American (AMR) AF: 0.00 AC: 0 AN: 1342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2978

East Asian (EAS) AF: 0.00 AC: 0 AN: 3688

South Asian (SAS) AF: 0.00 AC: 0 AN: 7756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 860

European-Non Finnish (NFE) AF: 0.0000811 AC: 26 AN: 320744

Other (OTH) AF: 0.0000789 AC: 1 AN: 12674

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 129906 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 63084

African (AFR) AF: 0.00 AC: 0 AN: 34908

American (AMR) AF: 0.00 AC: 0 AN: 13610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3152

East Asian (EAS) AF: 0.00 AC: 0 AN: 4394

South Asian (SAS) AF: 0.00 AC: 0 AN: 3910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7166

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 59896

Other (OTH) AF: 0.00 AC: 0 AN: 1802

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15
Mutation Taster		=295/5	polymorphism

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

Other links and lift over

dbSNP: rs886056593; hg19: chr20-30946488;