NM_001379451.1:c.214C>T

Variant names:

• chrX-130012986-C-T
• rs141901231
• NM_001379451.1:c.214C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001379451.1(BCORL1):​c.214C>T​(p.Arg72Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000512 in 1,201,146 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 174 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., 11 hem., cov: 24)
  • Exomes 𝑓: 0.00053 (0 hom. 163 hem.)
• Consequence: BCORL1 NM_001379451.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.58
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• Shukla-Vernon syndrome

  Inheritance: XL Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Illumina, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14974695).
• BP6: Variant X-130012986-C-T is Benign according to our data. Variant chrX-130012986-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2661409.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 40 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379451.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCORL1	NM_001379451.1	MANE Select	c.214C>T	p.Arg72Trp	missense	Exon 4 of 14	NP_001366380.1	Q5H9F3-3
	BCORL1	NM_001184772.3		c.214C>T	p.Arg72Trp	missense	Exon 5 of 15	NP_001171701.1	Q5H9F3-3
	BCORL1	NM_001379450.1		c.214C>T	p.Arg72Trp	missense	Exon 4 of 14	NP_001366379.1	Q5H9F3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCORL1	ENST00000540052.6	TSL:1 MANE Select	c.214C>T	p.Arg72Trp	missense	Exon 4 of 14	ENSP00000437775.2	Q5H9F3-3
	BCORL1	ENST00000218147.11	TSL:5	c.214C>T	p.Arg72Trp	missense	Exon 4 of 13	ENSP00000218147.7	Q5H9F3-1
	BCORL1	ENST00000488135.6	TSL:3	n.*232C>T		non_coding_transcript_exon	Exon 6 of 6	ENSP00000476643.1	V9GYD4

Frequencies

GnomAD3 genomes AF: 0.000354 AC: 40 AN: 112847 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000354

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000187

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000507

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000191 AC: 33 AN: 173006 AF XY: 0.000198

Gnomad AFR exome AF: 0.0000807

Gnomad AMR exome AF: 0.000189

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000351

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000528 AC: 575 AN: 1088299 Hom.: 0 Cov.: 32 AF XY: 0.000458 AC XY: 163 AN XY: 355699

African (AFR) AF: 0.0000762 AC: 2 AN: 26230

American (AMR) AF: 0.000144 AC: 5 AN: 34709

Ashkenazi Jewish (ASJ) AF: 0.0000527 AC: 1 AN: 18972

East Asian (EAS) AF: 0.00 AC: 0 AN: 30011

South Asian (SAS) AF: 0.0000376 AC: 2 AN: 53242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40139

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4092

European-Non Finnish (NFE) AF: 0.000669 AC: 559 AN: 835297

Other (OTH) AF: 0.000132 AC: 6 AN: 45607

GnomAD4 genome AF: 0.000354 AC: 40 AN: 112847 Hom.: 0 Cov.: 24 AF XY: 0.000314 AC XY: 11 AN XY: 35015

African (AFR) AF: 0.000354 AC: 11 AN: 31101

American (AMR) AF: 0.000187 AC: 2 AN: 10720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3600

South Asian (SAS) AF: 0.00 AC: 0 AN: 2780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6257

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.000507 AC: 27 AN: 53299

Other (OTH) AF: 0.00 AC: 0 AN: 1514

Alfa AF: 0.000460 Hom.: 21

Bravo AF: 0.000329

ESP6500AA AF: 0.000262 AC: 1

ESP6500EA AF: 0.000746 AC: 5

ExAC AF: 0.000206 AC: 25

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.77	T
PhyloP100		5.6
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.16
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.022	D
Vest4		0.46
MVP		0.56
MPC		0.43
ClinPred		0.11	T
GERP RS		5.3
gMVP		0.090
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs141901231; hg19: chrX-129146962; COSMIC: COSV99500030; COSMIC: COSV99500030;