rs2056443

Positions:

• chr13-31331805-T-C
• chr13-31331805-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_194318.4(B3GLCT):​c.*2137T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,110 control chromosomes in the GnomAD database, including 34,719 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (34719 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: B3GLCT NM_194318.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.781

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 13-31331805-T-C is Benign according to our data. Variant chr13-31331805-T-C is described in ClinVar as [Benign]. Clinvar id is 880654.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B3GLCT	NM_194318.4	c.*2137T>C		3_prime_UTR_variant	15/15	ENST00000343307.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GLCT	ENST00000343307.5	c.*2137T>C		3_prime_UTR_variant	15/15	1	NM_194318.4	P1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100834 AN: 151992 Hom.: 34718 Cov.: 33

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.673

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.663 AC: 100877 AN: 152110 Hom.: 34719 Cov.: 33 AF XY: 0.659 AC XY: 48997 AN XY: 74354

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.758

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.670

Alfa AF: 0.743 Hom.: 42930

Bravo AF: 0.656

Asia WGS AF: 0.625 AC: 2174 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Peters plus syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.85

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: rs2056443; hg19: chr13-31905942;