Variant chr20-32358753-TGCC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6BS2_Supporting

The NM_015338.6(ASXL1):c.-12_-10delCCG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000615 in 1,057,328 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0000071 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000061 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ASXL1
NM_015338.6 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.15

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 Likely_benign. Variant got -2 ACMG points.

BP6

Variant 20-32358753-TGCC-T is Benign according to our data. Variant chr20-32358753-TGCC-T is described in ClinVar as [Likely_benign]. Clinvar id is 3045967.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAdExome4 at 65 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
ASXL1	NM_015338.6 link	c.-12_-10delCCG	5_prime_UTR_variant	1/13	ENST00000375687.10	NP_056153.2	Q8IXJ9-1
ASXL1	NM_001164603.1 link	c.-12_-10delCCG	5_prime_UTR_variant	1/5		NP_001158075.1	Q498B9
ASXL1	XM_006723727.4 link	c.-12_-10delCCG	5_prime_UTR_variant	1/12		XP_006723790.1
ASXL1	XM_047439945.1 link	c.-12_-10delCCG	5_prime_UTR_variant	1/11		XP_047295901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASXL1	ENST00000375687 link	c.-12_-10delCCG		5_prime_UTR_variant	1/13	5	NM_015338.6	ENSP00000364839.4		Q8IXJ9-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

141584

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000260

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:

0.0000615

AC:

AN:

1057328

Hom.:

AF XY:

0.0000703

AC XY:

AN XY:

526230

show subpopulations

Gnomad4 AFR exome

AF:

0.0000986

Gnomad4 AMR exome

AF:

0.000110

Gnomad4 ASJ exome

AF:

0.000111

Gnomad4 EAS exome

AF:

0.000250

Gnomad4 SAS exome

AF:

0.0000991

Gnomad4 FIN exome

AF:

0.0000292

Gnomad4 NFE exome

AF:

0.0000535

Gnomad4 OTH exome

AF:

0.0000241

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000706

AC:

AN:

141584

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

68814

show subpopulations

Gnomad4 AFR

AF:

0.0000260

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000328

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ASXL1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 21, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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