dbSNP rs530763476: ASXL1:c.-282C>G (chr20-32358494-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015338.6(ASXL1):c.-282C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 79,284 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

ASXL1
NM_015338.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.560

Publications

0 publications found

Variant links:

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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Laboratory for Molecular Medicine, G2P, Illumina

ASXL1 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

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.-282C>G		5_prime_UTR	Exon 1 of 13	NP_056153.2
	ASXL1	NM_001164603.1		c.-282C>G		5_prime_UTR	Exon 1 of 5	NP_001158075.1	Q498B9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ASXL1	ENST00000375687.10	TSL:5 MANE Select	c.-282C>G	5_prime_UTR	Exon 1 of 13	ENSP00000364839.4	Q8IXJ9-1
ASXL1	ENST00000905973.1		c.-282C>G	5_prime_UTR	Exon 1 of 12	ENSP00000576032.1
ASXL1	ENST00000915088.1		c.-282C>G	5_prime_UTR	Exon 1 of 11	ENSP00000585147.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000126

AC:

AN:

79284

Hom.:

Cov.:

AF XY:

0.0000273

AC XY:

AN XY:

36564

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

3736

American (AMR)

AF:

0.00

AC:

AN:

2422

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4992

East Asian (EAS)

AF:

0.00

AC:

AN:

11294

South Asian (SAS)

AF:

0.00

AC:

AN:

1002

European-Finnish (FIN)

AF:

0.00

AC:

AN:

142

Middle Eastern (MID)

AF:

0.00

AC:

AN:

478

European-Non Finnish (NFE)

AF:

0.0000206

AC:

AN:

48636

Other (OTH)

AF:

0.00

AC:

AN:

6582

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

0.56

PromoterAI

0.012

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over