chrX-130005268-A-G

Variant names:

• chrX-130005268-A-G
• rs1928395845
• NM_001379451.1:c.37A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001379451.1(BCORL1):​c.37A>G​(p.Asn13Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,098,050 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: BCORL1 NM_001379451.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.09

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2730407).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCORL1	NM_001379451.1	c.37A>G	p.Asn13Asp	missense_variant	Exon 2 of 14	ENST00000540052.6	NP_001366380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCORL1	ENST00000540052.6	c.37A>G	p.Asn13Asp	missense_variant	Exon 2 of 14	1	NM_001379451.1	ENSP00000437775.2
BCORL1	ENST00000218147.11	c.37A>G	p.Asn13Asp	missense_variant	Exon 2 of 13	5		ENSP00000218147.7
BCORL1	ENST00000607874.1	c.37A>G	p.Asn13Asp	missense_variant	Exon 3 of 3	3		ENSP00000484149.1
BCORL1	ENST00000488135.6	n.37A>G		non_coding_transcript_exon_variant	Exon 3 of 6	3		ENSP00000476643.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1098050 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 1 AN XY: 363412

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: 0.00000119

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Dec 14, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 13 of the BCORL1 protein (p.Asn13Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BCORL1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Uncertain	0.99
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.67	T;.;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.3	.;N;N
REVEL	Benign	0.068
Sift	Uncertain	0.0050	.;D;D
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.32, 0.17
MutPred		0.22		Loss of MoRF binding (P = 0.0545);Loss of MoRF binding (P = 0.0545);Loss of MoRF binding (P = 0.0545);
MVP		0.65
MPC		0.47
ClinPred		0.48	T
GERP RS		3.5
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1928395845; hg19: chrX-129139244;