rs62206933

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_015338.6(ASXL1):c.2985C>T(p.His995=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,614,160 control chromosomes in the GnomAD database, including 671 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 123 hom., cov: 32)

Exomes 𝑓: 0.010 ( 548 hom. )

Consequence

ASXL1
NM_015338.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0210

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 20-32435697-C-T is Benign according to our data. Variant chr20-32435697-C-T is described in ClinVar as [Benign]. Clinvar id is 338104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-32435697-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.021 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASXL1	NM_015338.6 linkuse as main transcript	c.2985C>T	p.His995=	synonymous_variant	13/13	ENST00000375687.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASXL1	ENST00000375687.10 linkuse as main transcript	c.2985C>T	p.His995=	synonymous_variant	13/13	5	NM_015338.6	P1	Q8IXJ9-1

Frequencies

GnomAD3 genomes

AF:

0.0244

AC:

3718

AN:

152168

Hom.:

124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0443

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0865

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.0254

Gnomad SAS

AF:

0.0217

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00322

Gnomad OTH

AF:

0.0263

GnomAD3 exomes

AF:

0.0278

AC:

6982

AN:

251428

Hom.:

368

AF XY:

0.0231

AC XY:

3140

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0445

Gnomad AMR exome

AF:

0.128

Gnomad ASJ exome

AF:

0.0125

Gnomad EAS exome

AF:

0.0246

Gnomad SAS exome

AF:

0.0227

Gnomad FIN exome

AF:

0.000832

Gnomad NFE exome

AF:

0.00362

Gnomad OTH exome

AF:

0.0200

GnomAD4 exome

AF:

0.0104

AC:

15160

AN:

1461874

Hom.:

548

Cov.:

AF XY:

0.00996

AC XY:

7241

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0465

Gnomad4 AMR exome

AF:

0.124

Gnomad4 ASJ exome

AF:

0.0121

Gnomad4 EAS exome

AF:

0.0366

Gnomad4 SAS exome

AF:

0.0197

Gnomad4 FIN exome

AF:

0.000917

Gnomad4 NFE exome

AF:

0.00323

Gnomad4 OTH exome

AF:

0.0136

GnomAD4 genome

AF:

0.0244

AC:

3723

AN:

152286

Hom.:

123

Cov.:

AF XY:

0.0256

AC XY:

1907

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0443

Gnomad4 AMR

AF:

0.0865

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.0255

Gnomad4 SAS

AF:

0.0214

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00322

Gnomad4 OTH

AF:

0.0260

Alfa

AF:

0.0105

Hom.:

Bravo

AF:

0.0324

Asia WGS

AF:

0.0440

AC:

153

AN:

3478

EpiCase

AF:

0.00431

EpiControl

AF:

0.00498

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2018	- -

Bohring-Opitz syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

Cadd

Benign

5.8

Dann

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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