Variant 20-32358884-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015338.6(ASXL1):c.57+52C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00086 in 1,432,950 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 11 hom., cov: 31)

Exomes 𝑓: 0.00076 ( 15 hom. )

Consequence

ASXL1
NM_015338.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.64

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 20-32358884-C-T is Benign according to our data. Variant chr20-32358884-C-T is described in ClinVar as [Benign]. Clinvar id is 1228443.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00174 (264/151518) while in subpopulation EAS AF= 0.0474 (241/5088). AF 95% confidence interval is 0.0425. There are 11 homozygotes in gnomad4. There are 153 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd at 265 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ASXL1	NM_015338.6 linkuse as main transcript	c.57+52C>T	intron_variant	ENST00000375687.10
ASXL1	NM_001164603.1 linkuse as main transcript	c.57+52C>T	intron_variant
ASXL1	XM_006723727.4 linkuse as main transcript	c.57+52C>T	intron_variant
ASXL1	XM_047439945.1 linkuse as main transcript	c.57+52C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASXL1	ENST00000375687.10 linkuse as main transcript	c.57+52C>T		intron_variant		5	NM_015338.6	P1	Q8IXJ9-1

Frequencies

GnomAD3 genomes

AF:

0.00175

AC:

265

AN:

151412

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0476

Gnomad SAS

AF:

0.00146

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000443

Gnomad OTH

AF:

0.000482

GnomAD3 exomes

AF:

0.00267

AC:

160

AN:

59858

Hom.:

AF XY:

0.00243

AC XY:

AN XY:

33810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0487

Gnomad SAS exome

AF:

0.00125

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000635

GnomAD4 exome

AF:

0.000756

AC:

969

AN:

1281432

Hom.:

Cov.:

AF XY:

0.000765

AC XY:

482

AN XY:

629762

show subpopulations

Gnomad4 AFR exome

AF:

0.0000786

Gnomad4 AMR exome

AF:

0.0000950

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0269

Gnomad4 SAS exome

AF:

0.00127

Gnomad4 FIN exome

AF:

0.0000224

Gnomad4 NFE exome

AF:

0.00000784

Gnomad4 OTH exome

AF:

0.00182

GnomAD4 genome

AF:

0.00174

AC:

264

AN:

151518

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

153

AN XY:

74038

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0474

Gnomad4 SAS

AF:

0.00167

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000443

Gnomad4 OTH

AF:

0.000477

Alfa

AF:

0.000419

Hom.:

Bravo

AF:

0.00230

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 23, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

Cadd

Benign

5.7

Dann

Benign

0.75

RBP_binding_hub_radar

0.91

RBP_regulation_power_radar

2.2

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over