rs117111131

Positions:

• chr13-31247011-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000343307.5(B3GLCT):​c.271-12T>C 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 0.0239 in 1,597,596 control chromosomes in the GnomAD database, including 579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (38 hom., cov: 28)
  • Exomes 𝑓: 0.024 (541 hom.)
• Consequence: B3GLCT ENST00000343307.5 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00008837
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.256

Genes affected

B3GLCT (HGNC:20207): (beta 3-glucosyltransferase) The protein encoded by this gene is a beta-1,3-glucosyltransferase that transfers glucose to O-linked fucosylglycans on thrombospondin type-1 repeats (TSRs) of several proteins. The encoded protein is a type II membrane protein. Defects in this gene are a cause of Peters-plus syndrome (PPS).[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 13-31247011-T-C is Benign according to our data. Variant chr13-31247011-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 96625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-31247011-T-C is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0186 (2812/151098) while in subpopulation NFE AF= 0.0263 (1787/67856). AF 95% confidence interval is 0.0253. There are 38 homozygotes in gnomad4. There are 1293 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GLCT	NM_194318.4	c.271-12T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000343307.5	NP_919299.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GLCT	ENST00000343307.5	c.271-12T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_194318.4	ENSP00000343002	P1

Frequencies

GnomAD3 genomes AF: 0.0186 AC: 2814 AN: 150988 Hom.: 38 Cov.: 28

Gnomad AFR AF: 0.00526

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0216

Gnomad ASJ AF: 0.0737

Gnomad EAS AF: 0.000394

Gnomad SAS AF: 0.00526

Gnomad FIN AF: 0.0123

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.0252

GnomAD3 exomes AF: 0.0214 AC: 5368 AN: 251274 Hom.: 88 AF XY: 0.0217 AC XY: 2948 AN XY: 135796

Gnomad AFR exome AF: 0.00418

Gnomad AMR exome AF: 0.0172

Gnomad ASJ exome AF: 0.0718

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00817

Gnomad FIN exome AF: 0.0160

Gnomad NFE exome AF: 0.0282

Gnomad OTH exome AF: 0.0294

GnomAD4 exome AF: 0.0245 AC: 35404 AN: 1446498 Hom.: 541 Cov.: 31 AF XY: 0.0245 AC XY: 17636 AN XY: 720648

Gnomad4 AFR exome AF: 0.00488

Gnomad4 AMR exome AF: 0.0176

Gnomad4 ASJ exome AF: 0.0759

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.00786

Gnomad4 FIN exome AF: 0.0159

Gnomad4 NFE exome AF: 0.0266

Gnomad4 OTH exome AF: 0.0258

GnomAD4 genome AF: 0.0186 AC: 2812 AN: 151098 Hom.: 38 Cov.: 28 AF XY: 0.0175 AC XY: 1293 AN XY: 73802

Gnomad4 AFR AF: 0.00524

Gnomad4 AMR AF: 0.0215

Gnomad4 ASJ AF: 0.0737

Gnomad4 EAS AF: 0.000395

Gnomad4 SAS AF: 0.00527

Gnomad4 FIN AF: 0.0123

Gnomad4 NFE AF: 0.0263

Gnomad4 OTH AF: 0.0249

Alfa AF: 0.0274 Hom.: 9

Bravo AF: 0.0199

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Peters plus syndrome Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 18, 2013	- -

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Likely 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	-0.84
CADD	Benign	0.020
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000088
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.17		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: rs117111131; hg19: chr13-31821148;