rs1325772447

Variant names:

• chrX-130005259-G-A
• rs1325772447
• NM_001379451.1:c.28G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-130005259-G-A
• chrX-130005259-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BS2_Supporting

The NM_001379451.1(BCORL1):​c.28G>A​(p.Gly10Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000578 in 1,210,148 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G10G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000055 (0 hom. 1 hem.)
• Consequence: BCORL1 NM_001379451.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.83
• Publications: 0 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 -3 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16930732).
• BS2: High AC in GnomAdExome4 at 6 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.28G>A	p.Gly10Ser	missense	Exon 2 of 14	NP_001366380.1	Q5H9F3-3
	BCORL1	NM_001184772.3		c.28G>A	p.Gly10Ser	missense	Exon 3 of 15	NP_001171701.1	Q5H9F3-3
	BCORL1	NM_001379450.1		c.28G>A	p.Gly10Ser	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.28G>A	p.Gly10Ser	missense	Exon 2 of 14	ENSP00000437775.2	Q5H9F3-3
	BCORL1	ENST00000218147.11	TSL:5	c.28G>A	p.Gly10Ser	missense	Exon 2 of 13	ENSP00000218147.7	Q5H9F3-1
	BCORL1	ENST00000607874.1	TSL:3	c.28G>A	p.Gly10Ser	missense	Exon 3 of 3	ENSP00000484149.1	A0A087X1F0

Frequencies

GnomAD3 genomes AF: 0.00000891 AC: 1 AN: 112178 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000546 AC: 1 AN: 183253 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000546 AC: 6 AN: 1097970 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 1 AN XY: 363344

African (AFR) AF: 0.00 AC: 0 AN: 26399

American (AMR) AF: 0.0000284 AC: 1 AN: 35195

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19382

East Asian (EAS) AF: 0.00 AC: 0 AN: 30195

South Asian (SAS) AF: 0.00 AC: 0 AN: 54108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00000594 AC: 5 AN: 841963

Other (OTH) AF: 0.00 AC: 0 AN: 46076

GnomAD4 genome AF: 0.00000891 AC: 1 AN: 112178 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34344

African (AFR) AF: 0.00 AC: 0 AN: 30832

American (AMR) AF: 0.00 AC: 0 AN: 10548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3601

South Asian (SAS) AF: 0.00 AC: 0 AN: 2738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6121

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53257

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.15
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Uncertain	0.99
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.98	T
PhyloP100		2.8
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.045
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Vest4		0.36
MutPred		0.27		Gain of disorder (P = 0.0407)
MVP		0.45
MPC		0.41
ClinPred		0.66	D
GERP RS		3.9
gMVP		0.53
Mutation Taster		=82/18	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: rs1325772447; hg19: chrX-129139235;