chr18-33607946-C-A

Position:

• chr18-33607946-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030632.3(ASXL3):​c.137+270C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,736 control chromosomes in the GnomAD database, including 8,118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (8118 hom., cov: 32)
• Consequence: ASXL3 NM_030632.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.989

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 18-33607946-C-A is Benign according to our data. Variant chr18-33607946-C-A is described in ClinVar as [Benign]. Clinvar id is 1227429.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASXL3	NM_030632.3	c.137+270C>A		intron_variant		ENST00000269197.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASXL3	ENST00000269197.12	c.137+270C>A		intron_variant		5	NM_030632.3	P4

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45009 AN: 151616 Hom.: 8124 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.0612

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.296 AC: 44989 AN: 151736 Hom.: 8118 Cov.: 32 AF XY: 0.292 AC XY: 21636 AN XY: 74130

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.0607

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.341

Alfa AF: 0.374 Hom.: 7102

Bravo AF: 0.284

Asia WGS AF: 0.168 AC: 586 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.37

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: rs726145; hg19: chr18-31187910;