X-130005320-GA-G

Variant names:

• chrX-130005320-GA-G
• NM_001379451.1:c.86+4delA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001379451.1(BCORL1):​c.86+4delA variant causes a splice region, intron change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: BCORL1 NM_001379451.1 splice_region, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.65

Genes affected

BCORL1 (HGNC:25657): (BCL6 corepressor like 1) The protein encoded by this gene is a transcriptional corepressor that is found tethered to promoter regions by DNA-binding proteins. The encoded protein can interact with several different class II histone deacetylases to repress transcription. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCORL1	NM_001379451.1	c.86+4delA		splice_region_variant, intron_variant	Intron 2 of 13	ENST00000540052.6	NP_001366380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCORL1	ENST00000540052.6	c.86+4delA		splice_region_variant, intron_variant	Intron 2 of 13	1	NM_001379451.1	ENSP00000437775.2
BCORL1	ENST00000218147.11	c.86+4delA		splice_region_variant, intron_variant	Intron 2 of 12	5		ENSP00000218147.7
BCORL1	ENST00000488135.6	n.86+4delA		splice_region_variant, intron_variant	Intron 3 of 5	3		ENSP00000476643.1
BCORL1	ENST00000607874.1	c.*4delA		downstream_gene_variant		3		ENSP00000484149.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Oct 03, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.44		Position offset: 34

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-129139296;