rs743641

Variant names:

• chrX-153508696-A-T
• rs743641
• NM_001711.6:c.*251A>T

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.*251A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 416,935 control chromosomes in the GnomAD database, including 6,555 homozygotes. There are 22,643 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (2944 hom., 7372 hem., cov: 23)
  • Exomes 𝑓: 0.15 (3611 hom. 15271 hem.)
• Consequence: BGN NM_001711.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.08
• Publications: 8 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=-0.87).
• BP6: Variant X-153508696-A-T is Benign according to our data. Variant chrX-153508696-A-T is described in ClinVar as Benign. ClinVar VariationId is 1233314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BGN	NM_001711.6	c.*251A>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000331595.9	NP_001702.1
BGN	XM_017029724.3	c.*251A>T		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.*251A>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_001711.6	ENSP00000327336.4
BGN	ENST00000472615.5	n.1375A>T		non_coding_transcript_exon_variant	Exon 8 of 8	5
BGN	ENST00000480756.1	n.1428A>T		non_coding_transcript_exon_variant	Exon 8 of 8	5
BGN	ENST00000492658.1	n.311A>T		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.221 AC: 24545 AN: 110990 Hom.: 2941 Cov.: 23

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.0929

Gnomad MID AF: 0.132

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.245

GnomAD4 exome AF: 0.147 AC: 45015 AN: 305896 Hom.: 3611 Cov.: 3 AF XY: 0.158 AC XY: 15271 AN XY: 96558

African (AFR) AF: 0.413 AC: 3785 AN: 9168

American (AMR) AF: 0.467 AC: 5725 AN: 12256

Ashkenazi Jewish (ASJ) AF: 0.0363 AC: 337 AN: 9292

East Asian (EAS) AF: 0.292 AC: 6244 AN: 21397

South Asian (SAS) AF: 0.281 AC: 6923 AN: 24631

European-Finnish (FIN) AF: 0.0925 AC: 1956 AN: 21138

Middle Eastern (MID) AF: 0.128 AC: 168 AN: 1313

European-Non Finnish (NFE) AF: 0.0887 AC: 16693 AN: 188110

Other (OTH) AF: 0.171 AC: 3184 AN: 18591

GnomAD4 genome AF: 0.221 AC: 24562 AN: 111039 Hom.: 2944 Cov.: 23 AF XY: 0.221 AC XY: 7372 AN XY: 33333

African (AFR) AF: 0.414 AC: 12581 AN: 30412

American (AMR) AF: 0.409 AC: 4320 AN: 10554

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 95 AN: 2638

East Asian (EAS) AF: 0.348 AC: 1209 AN: 3471

South Asian (SAS) AF: 0.273 AC: 723 AN: 2649

European-Finnish (FIN) AF: 0.0929 AC: 564 AN: 6069

Middle Eastern (MID) AF: 0.140 AC: 30 AN: 214

European-Non Finnish (NFE) AF: 0.0858 AC: 4533 AN: 52850

Other (OTH) AF: 0.242 AC: 364 AN: 1507

Alfa AF: 0.157 Hom.: 918

Bravo AF: 0.258

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 10, 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	-0.87
CADD	Benign	0.30
DANN	Benign	0.17
PhyloP100		-1.1
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: rs743641; hg19: chrX-152774154;