chrX-130005293-G-A

Variant names:

• chrX-130005293-G-A
• rs778701486
• NM_001379451.1:c.62G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4 BP6_Moderate BS2_Supporting

The NM_001379451.1(BCORL1):​c.62G>A​(p.Arg21His) variant causes a missense change. The variant allele was found at a frequency of 0.000132 in 1,209,942 control chromosomes in the GnomAD database, including 1 homozygotes. There are 49 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (1 hom., 6 hem., cov: 22)
  • Exomes 𝑓: 0.00013 (0 hom. 43 hem.)
• Consequence: BCORL1 NM_001379451.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter U:2 B:1
• Conservation: PhyloP100: 7.11
• Publications: 10 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.35522416).
• BP6: Variant X-130005293-G-A is Benign according to our data. Variant chrX-130005293-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1299882.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 18 XL,AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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.62G>A	p.Arg21His	missense	Exon 2 of 14	NP_001366380.1	Q5H9F3-3
	BCORL1	NM_001184772.3		c.62G>A	p.Arg21His	missense	Exon 3 of 15	NP_001171701.1	Q5H9F3-3
	BCORL1	NM_001379450.1		c.62G>A	p.Arg21His	missense	Exon 2 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.62G>A	p.Arg21His	missense	Exon 2 of 14	ENSP00000437775.2	Q5H9F3-3
	BCORL1	ENST00000218147.11	TSL:5	c.62G>A	p.Arg21His	missense	Exon 2 of 13	ENSP00000218147.7	Q5H9F3-1
	BCORL1	ENST00000607874.1	TSL:3	c.62G>A	p.Arg21His	missense	Exon 3 of 3	ENSP00000484149.1	A0A087X1F0

Frequencies

GnomAD3 genomes AF: 0.000160 AC: 18 AN: 112180 Hom.: 1 Cov.: 22

Gnomad AFR AF: 0.0000972

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000190

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: 0.000244

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000819 AC: 15 AN: 183246 AF XY: 0.0000443

Gnomad AFR exome AF: 0.0000760

Gnomad AMR exome AF: 0.000109

Gnomad ASJ exome AF: 0.000401

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000979

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000129 AC: 142 AN: 1097762 Hom.: 0 Cov.: 30 AF XY: 0.000118 AC XY: 43 AN XY: 363138

African (AFR) AF: 0.0000758 AC: 2 AN: 26393

American (AMR) AF: 0.0000852 AC: 3 AN: 35201

Ashkenazi Jewish (ASJ) AF: 0.000155 AC: 3 AN: 19378

East Asian (EAS) AF: 0.00 AC: 0 AN: 30191

South Asian (SAS) AF: 0.00 AC: 0 AN: 54107

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40515

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.000152 AC: 128 AN: 841772

Other (OTH) AF: 0.000130 AC: 6 AN: 46070

GnomAD4 genome AF: 0.000160 AC: 18 AN: 112180 Hom.: 1 Cov.: 22 AF XY: 0.000175 AC XY: 6 AN XY: 34322

African (AFR) AF: 0.0000972 AC: 3 AN: 30873

American (AMR) AF: 0.000190 AC: 2 AN: 10543

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3592

South Asian (SAS) AF: 0.00 AC: 0 AN: 2719

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6111

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.000244 AC: 13 AN: 53258

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

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.000102

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	2	1	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.36	T
MetaSVM	Uncertain	-0.062	T
PhyloP100		7.1
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.50
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Vest4		0.58
MVP		0.91
MPC		0.52
ClinPred		0.14	T
GERP RS		4.7
gMVP		0.45
Mutation Taster		=93/7	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: rs778701486; hg19: chrX-129139269; COSMIC: COSV54393535;