NM_194318.4:c.*2336A>C

Variant names:

• chr13-31332004-A-C
• rs13080
• NM_194318.4:c.*2336A>C

Variant summary

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

The NM_194318.4(B3GLCT):​c.*2336A>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 0.67 in 152,002 control chromosomes in the GnomAD database, including 35,149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (35149 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: B3GLCT NM_194318.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.52
• Publications: 22 publications found

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]

B3GLCT Gene-Disease associations (from GenCC):

• Peters plus syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, G2P, PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 13-31332004-A-C is Benign according to our data. Variant chr13-31332004-A-C is described in ClinVar as [Benign]. Clinvar id is 880658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GLCT	NM_194318.4	c.*2336A>C		3_prime_UTR_variant	Exon 15 of 15	ENST00000343307.5	NP_919299.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GLCT	ENST00000343307.5	c.*2336A>C		3_prime_UTR_variant	Exon 15 of 15	1	NM_194318.4	ENSP00000343002.4

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101738 AN: 151884 Hom.: 35149 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.676

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.670 AC: 101780 AN: 152002 Hom.: 35149 Cov.: 32 AF XY: 0.665 AC XY: 49431 AN XY: 74306

African (AFR) AF: 0.500 AC: 20732 AN: 41450

American (AMR) AF: 0.691 AC: 10560 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2629 AN: 3470

East Asian (EAS) AF: 0.572 AC: 2954 AN: 5160

South Asian (SAS) AF: 0.656 AC: 3161 AN: 4816

European-Finnish (FIN) AF: 0.684 AC: 7227 AN: 10568

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52070 AN: 67952

Other (OTH) AF: 0.673 AC: 1418 AN: 2106

Alfa AF: 0.728 Hom.: 108017

Bravo AF: 0.664

Asia WGS AF: 0.626 AC: 2178 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Peters plus syndrome Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.77
DANN	Benign	0.56
PhyloP100		-2.5
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: rs13080; hg19: chr13-31906141;