18-33686777-A-G

Position:

• chr18-33686777-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030632.3(ASXL3):​c.879+3209A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 152,058 control chromosomes in the GnomAD database, including 25,014 homozygotes. 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: 𝑓 0.57 (25014 hom., cov: 32)
• Consequence: ASXL3 NM_030632.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.632

Genes affected

ASXL3 (HGNC:29357): (ASXL transcriptional regulator 3) This gene encodes a protein containing a plant homeodomain (PHD) zinc finger domain that plays a role in the regulation of gene transcription. The encoded protein has been shown to negatively regulate lipogenesis by binding to and inhibiting the transcriptional activity of two nuclear hormone receptors, oxysterols receptor LXR-alpha (LXRalpha) and thyroid hormone receptor beta (TRbeta). The encoded protein may also inhibit histone deubiquitination. Mutations in this gene have been identified in human patients with Bainbridge-Ropers syndrome, which is characterized by feeding difficulties, developmental delay and other features. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASXL3	NM_030632.3	c.879+3209A>G		intron_variant		ENST00000269197.12	NP_085135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASXL3	ENST00000269197.12	c.879+3209A>G		intron_variant		5	NM_030632.3	ENSP00000269197.4

Frequencies

GnomAD3 genomes AF: 0.566 AC: 86001 AN: 151940 Hom.: 24980 Cov.: 32

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.535

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.566 AC: 86091 AN: 152058 Hom.: 25014 Cov.: 32 AF XY: 0.570 AC XY: 42337 AN XY: 74328

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.900

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.537

Alfa AF: 0.506 Hom.: 17676

Bravo AF: 0.578

Asia WGS AF: 0.698 AC: 2424 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.3
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs4799710; hg19: chr18-31266741;