chrX-130012986-CG-C

Variant names:

• chrX-130012986-CG-C
• rs779498199
• NM_001379451.1:c.220delG

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001379451.1(BCORL1):​c.220delG​(p.Ala74GlnfsTer42) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: BCORL1 NM_001379451.1 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.67

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 Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• 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.220delG	p.Ala74GlnfsTer42	frameshift_variant	Exon 4 of 14	ENST00000540052.6	NP_001366380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCORL1	ENST00000540052.6	c.220delG	p.Ala74GlnfsTer42	frameshift_variant	Exon 4 of 14	1	NM_001379451.1	ENSP00000437775.2
BCORL1	ENST00000218147.11	c.220delG	p.Ala74GlnfsTer42	frameshift_variant	Exon 4 of 13	5		ENSP00000218147.7
BCORL1	ENST00000488135.6	n.*238delG		non_coding_transcript_exon_variant	Exon 6 of 6	3		ENSP00000476643.1
BCORL1	ENST00000488135.6	n.*238delG		3_prime_UTR_variant	Exon 6 of 6	3		ENSP00000476643.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1088283 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 355689

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Mar 02, 2016

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.220delG variant in the BCORL1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.220delG variant causes a frameshift starting with codon Alanine 74, changes this amino acid to a Glutamine residue, and creates a premature Stop codon at position 42 of the new reading frame, denoted p.A74QfsX42. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.220delG variant was not observed in approximately 6400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.220delG as a variant of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

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: rs779498199; hg19: chrX-129146962;