Variant chrX-153504606-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000331595.9(BGN):c.-11-15C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000896 in 1,151,918 control chromosomes in the GnomAD database, including 12 homozygotes. There are 294 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 0.00081 ( 2 hom., 25 hem., cov: 25)

Exomes 𝑓: 0.00091 ( 10 hom. 269 hem. )

Consequence

BGN
ENST00000331595.9 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.94

Variant links:

Genes affected

BGN (HGNC:1044): (biglycan) This gene encodes a member of the small leucine-rich proteoglycan (SLRP) family of proteins. The encoded preproprotein is proteolytically processed to generate the mature protein, which plays a role in bone growth, muscle development and regeneration, and collagen fibril assembly in multiple tissues. This protein may also regulate inflammation and innate immunity. Additionally, the encoded protein may contribute to atherosclerosis and aortic valve stenosis in human patients. This gene and the related gene decorin are thought to be the result of a gene duplication. [provided by RefSeq, Nov 2015]

BGN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant X-153504606-C-G is Benign according to our data. Variant chrX-153504606-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1316494.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000806 (91/112845) while in subpopulation EAS AF= 0.0235 (83/3532). AF 95% confidence interval is 0.0194. There are 2 homozygotes in gnomad4. There are 25 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BGN	NM_001711.6 linkuse as main transcript	c.-11-15C>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000331595.9	NP_001702.1
BGN	XM_017029724.3 linkuse as main transcript			upstream_gene_variant			XP_016885213.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
BGN	ENST00000331595.9 linkuse as main transcript	c.-11-15C>G	splice_polypyrimidine_tract_variant, intron_variant	1	NM_001711.6	ENSP00000327336	P1
BGN	ENST00000431891.1 linkuse as main transcript	c.-11-15C>G	splice_polypyrimidine_tract_variant, intron_variant	5		ENSP00000402525
BGN	ENST00000472615.5 linkuse as main transcript	n.134-15C>G	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	5
BGN	ENST00000480756.1 linkuse as main transcript	n.132-15C>G	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.000807

AC:

AN:

112792

Hom.:

Cov.:

AF XY:

0.000715

AC XY:

AN XY:

34948

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000186

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0234

Gnomad SAS

AF:

0.00108

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000563

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00233

AC:

377

AN:

161854

Hom.:

AF XY:

0.00224

AC XY:

115

AN XY:

51344

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000397

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0272

Gnomad SAS exome

AF:

0.000537

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00126

GnomAD4 exome

AF:

0.000906

AC:

941

AN:

1039073

Hom.:

Cov.:

AF XY:

0.000827

AC XY:

269

AN XY:

325357

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000596

Gnomad4 ASJ exome

AF:

0.0000558

Gnomad4 EAS exome

AF:

0.0288

Gnomad4 SAS exome

AF:

0.000493

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000628

Gnomad4 OTH exome

AF:

0.00116

GnomAD4 genome

AF:

0.000806

AC:

AN:

112845

Hom.:

Cov.:

AF XY:

0.000714

AC XY:

AN XY:

35011

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000185

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0235

Gnomad4 SAS

AF:

0.00109

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000563

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000109

Hom.:

Bravo

AF:

0.00143

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.2

DANN

Benign

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over