Variant 20-32358494-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_015338.6(ASXL1):c.-282C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00887 in 230,060 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0093 ( 12 hom., cov: 31)

Exomes 𝑓: 0.0081 ( 10 hom. )

Consequence

ASXL1
NM_015338.6 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.560

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 20-32358494-C-T is Benign according to our data. Variant chr20-32358494-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 338062.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00927 (1397/150782) while in subpopulation NFE AF= 0.0115 (775/67564). AF 95% confidence interval is 0.0108. There are 12 homozygotes in gnomad4. There are 729 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1397 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
ASXL1	NM_015338.6 linkuse as main transcript	c.-282C>T	5_prime_UTR_variant	1/13	ENST00000375687.10
ASXL1	NM_001164603.1 linkuse as main transcript	c.-282C>T	5_prime_UTR_variant	1/5
ASXL1	XM_006723727.4 linkuse as main transcript	c.-282C>T	5_prime_UTR_variant	1/12
ASXL1	XM_047439945.1 linkuse as main transcript	c.-282C>T	5_prime_UTR_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASXL1	ENST00000375687.10 linkuse as main transcript	c.-282C>T		5_prime_UTR_variant	1/13	5	NM_015338.6	P1	Q8IXJ9-1

Frequencies

GnomAD3 genomes

AF:

0.00927

AC:

1396

AN:

150674

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.00936

Gnomad ASJ

AF:

0.00665

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0346

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0115

Gnomad OTH

AF:

0.0102

GnomAD4 exome

AF:

0.00812

AC:

644

AN:

79278

Hom.:

Cov.:

AF XY:

0.00796

AC XY:

291

AN XY:

36562

show subpopulations

Gnomad4 AFR exome

AF:

0.00187

Gnomad4 AMR exome

AF:

0.00950

Gnomad4 ASJ exome

AF:

0.00381

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00399

Gnomad4 FIN exome

AF:

0.0357

Gnomad4 NFE exome

AF:

0.0108

Gnomad4 OTH exome

AF:

0.00851

GnomAD4 genome

AF:

0.00927

AC:

1397

AN:

150782

Hom.:

Cov.:

AF XY:

0.00990

AC XY:

729

AN XY:

73650

show subpopulations

Gnomad4 AFR

AF:

0.00155

Gnomad4 AMR

AF:

0.00935

Gnomad4 ASJ

AF:

0.00665

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0346

Gnomad4 NFE

AF:

0.0115

Gnomad4 OTH

AF:

0.0101

Alfa

AF:

0.0123

Hom.:

Bravo

AF:

0.00721

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.95

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

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