X-130013052-G-A

Variant names:

• chrX-130013052-G-A
• rs139887979
• NM_001379451.1:c.280G>A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001379451.1(BCORL1):​c.280G>A​(p.Asp94Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000648 in 1,209,618 control chromosomes in the GnomAD database, including 1 homozygotes. There are 241 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00067 (0 hom., 21 hem., cov: 24)
  • Exomes 𝑓: 0.00065 (1 hom. 220 hem.)
• Consequence: BCORL1 NM_001379451.1 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.37

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0053094625).
• BP6: Variant X-130013052-G-A is Benign according to our data. Variant chrX-130013052-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 735336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-130013052-G-A is described in Lovd as [Likely_benign].
• BS2: High Hemizygotes in GnomAd4 at 21 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCORL1	NM_001379451.1	c.280G>A	p.Asp94Asn	missense_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.280G>A	p.Asp94Asn	missense_variant	Exon 4 of 14	1	NM_001379451.1	ENSP00000437775.2
BCORL1	ENST00000218147.11	c.280G>A	p.Asp94Asn	missense_variant	Exon 4 of 13	5		ENSP00000218147.7
BCORL1	ENST00000488135.6	n.*298G>A		non_coding_transcript_exon_variant	Exon 6 of 6	3		ENSP00000476643.1
BCORL1	ENST00000488135.6	n.*298G>A		3_prime_UTR_variant	Exon 6 of 6	3		ENSP00000476643.1

Frequencies

GnomAD3 genomes AF: 0.000666 AC: 75 AN: 112574 Hom.: 0 Cov.: 24 AF XY: 0.000604 AC XY: 21 AN XY: 34744

Gnomad AFR AF: 0.000258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00244

Gnomad ASJ AF: 0.00113

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0126

Gnomad NFE AF: 0.000619

Gnomad OTH AF: 0.00132

GnomAD3 exomes AF: 0.000839 AC: 153 AN: 182462 Hom.: 1 AF XY: 0.000978 AC XY: 66 AN XY: 67456

Gnomad AFR exome AF: 0.000153

Gnomad AMR exome AF: 0.00223

Gnomad ASJ exome AF: 0.00269

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000653

Gnomad OTH exome AF: 0.00377

GnomAD4 exome AF: 0.000646 AC: 709 AN: 1096992 Hom.: 1 Cov.: 32 AF XY: 0.000607 AC XY: 220 AN XY: 362482

Gnomad4 AFR exome AF: 0.000341

Gnomad4 AMR exome AF: 0.00227

Gnomad4 ASJ exome AF: 0.00284

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000370

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000565

Gnomad4 OTH exome AF: 0.00143

GnomAD4 genome AF: 0.000666 AC: 75 AN: 112626 Hom.: 0 Cov.: 24 AF XY: 0.000603 AC XY: 21 AN XY: 34806

Gnomad4 AFR AF: 0.000257

Gnomad4 AMR AF: 0.00244

Gnomad4 ASJ AF: 0.00113

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000619

Gnomad4 OTH AF: 0.00131

Alfa AF: 0.00112 Hom.: 49

Bravo AF: 0.00114

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000692 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.000642 AC: 78

EpiCase AF: 0.000982

EpiControl AF: 0.000652

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jul 21, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 01, 2018

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	18
DANN	Uncertain	0.99
FATHMM_MKL	Benign	0.41	N
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.0053	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.70	N;N
REVEL	Benign	0.044
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.053	T;T
Vest4		0.13
MVP		0.27
MPC		0.40
ClinPred		0.060	T
GERP RS		3.0
gMVP		0.12

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: rs139887979; hg19: chrX-129147028; COSMIC: COSV105870210; COSMIC: COSV105870210;