Genetic Variant NM_001379451.1:c.220dupG (chrX-130012986-C-CG) – ACMG Classification: Pathogenic (10 pts)

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_001379451.1(BCORL1):c.220dupG(p.Ala74GlyfsTer20) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 1,088,277 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

BCORL1
NM_001379451.1 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.67

Variant links:

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]

BCORL1 links:

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ACMG classification

Classification made for transcript

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 link	c.220dupG	p.Ala74GlyfsTer20	frameshift_variant	Exon 4 of 14	ENST00000540052.6	NP_001366380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BCORL1	ENST00000540052.6 link	c.220dupG	p.Ala74GlyfsTer20	frameshift_variant	Exon 4 of 14	1	NM_001379451.1	ENSP00000437775.2	Q5H9F3-3
BCORL1	ENST00000218147.11 link	c.220dupG	p.Ala74GlyfsTer20	frameshift_variant	Exon 4 of 13	5		ENSP00000218147.7	Q5H9F3-1
BCORL1	ENST00000488135.6 link	n.*238dupG		non_coding_transcript_exon_variant	Exon 6 of 6	3		ENSP00000476643.1	V9GYD4
BCORL1	ENST00000488135.6 link	n.*238dupG		3_prime_UTR_variant	Exon 6 of 6	3		ENSP00000476643.1	V9GYD4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000578

AC:

AN:

173006

Hom.:

AF XY:

0.0000165

AC XY:

AN XY:

60594

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000130

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000184

AC:

AN:

1088277

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

355683

show subpopulations

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:

0.00000239

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over