rs1042103

Variant names:

• chrX-153508573-G-A
• rs1042103
• NM_001711.6:c.*128G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001711.6(BGN):​c.*128G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 833,191 control chromosomes in the GnomAD database, including 38,897 homozygotes. There are 79,348 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (3641 hom., 8625 hem., cov: 23)
  • Exomes 𝑓: 0.36 (35256 hom. 70723 hem.)
• Consequence: BGN NM_001711.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.56
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• Meester-Loeys syndrome

  Inheritance: XL Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, Illumina, G2P
• X-linked spondyloepimetaphyseal dysplasia

  Inheritance: XL Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant X-153508573-G-A is Benign according to our data. Variant chrX-153508573-G-A is described in ClinVar as Benign. ClinVar VariationId is 1263317.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BGN	NM_001711.6	c.*128G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000331595.9	NP_001702.1
BGN	XM_017029724.3	c.*128G>A		3_prime_UTR_variant	Exon 7 of 7		XP_016885213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BGN	ENST00000331595.9	c.*128G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_001711.6	ENSP00000327336.4
BGN	ENST00000472615.5	n.1252G>A		non_coding_transcript_exon_variant	Exon 8 of 8	5
BGN	ENST00000480756.1	n.1305G>A		non_coding_transcript_exon_variant	Exon 8 of 8	5
BGN	ENST00000492658.1	n.295-107G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.266 AC: 29592 AN: 111109 Hom.: 3642 Cov.: 23

Gnomad AFR AF: 0.0827

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.0726

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.357 AC: 257908 AN: 722029 Hom.: 35256 Cov.: 11 AF XY: 0.374 AC XY: 70723 AN XY: 189055

African (AFR) AF: 0.0826 AC: 1471 AN: 17805

American (AMR) AF: 0.123 AC: 2656 AN: 21563

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 4375 AN: 13369

East Asian (EAS) AF: 0.0797 AC: 2025 AN: 25418

South Asian (SAS) AF: 0.216 AC: 7872 AN: 36500

European-Finnish (FIN) AF: 0.443 AC: 11315 AN: 25564

Middle Eastern (MID) AF: 0.266 AC: 552 AN: 2075

European-Non Finnish (NFE) AF: 0.397 AC: 217053 AN: 546637

Other (OTH) AF: 0.320 AC: 10589 AN: 33098

GnomAD4 genome AF: 0.266 AC: 29585 AN: 111162 Hom.: 3641 Cov.: 23 AF XY: 0.258 AC XY: 8625 AN XY: 33448

African (AFR) AF: 0.0826 AC: 2537 AN: 30712

American (AMR) AF: 0.170 AC: 1813 AN: 10668

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 833 AN: 2630

East Asian (EAS) AF: 0.0731 AC: 258 AN: 3529

South Asian (SAS) AF: 0.192 AC: 511 AN: 2656

European-Finnish (FIN) AF: 0.439 AC: 2586 AN: 5894

Middle Eastern (MID) AF: 0.282 AC: 60 AN: 213

European-Non Finnish (NFE) AF: 0.387 AC: 20403 AN: 52670

Other (OTH) AF: 0.230 AC: 348 AN: 1515

Alfa AF: 0.330 Hom.: 13131

Bravo AF: 0.240

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.44
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs1042103; hg19: chrX-152774031;