chrX-153508696-A-T

Position:

• chrX-153508696-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000331595.9(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 ENST00000331595.9 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.08

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
BGN	NM_001711.6	c.*251A>T		3_prime_UTR_variant	8/8	ENST00000331595.9	NP_001702.1
BGN	XM_017029724.3	c.*251A>T		3_prime_UTR_variant	7/7		XP_016885213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BGN	ENST00000331595.9	c.*251A>T		3_prime_UTR_variant	8/8	1	NM_001711.6	ENSP00000327336	P1
BGN	ENST00000472615.5	n.1375A>T		non_coding_transcript_exon_variant	8/8	5
BGN	ENST00000480756.1	n.1428A>T		non_coding_transcript_exon_variant	8/8	5
BGN	ENST00000492658.1	n.311A>T		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.221 AC: 24545 AN: 110990 Hom.: 2941 Cov.: 23 AF XY: 0.221 AC XY: 7357 AN XY: 33272

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

Gnomad4 AFR exome AF: 0.413

Gnomad4 AMR exome AF: 0.467

Gnomad4 ASJ exome AF: 0.0363

Gnomad4 EAS exome AF: 0.292

Gnomad4 SAS exome AF: 0.281

Gnomad4 FIN exome AF: 0.0925

Gnomad4 NFE exome AF: 0.0887

Gnomad4 OTH exome AF: 0.171

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

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.0360

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.0929

Gnomad4 NFE AF: 0.0858

Gnomad4 OTH AF: 0.242

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.30
DANN	Benign	0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs743641; hg19: chrX-152774154;