Genetic Variant B3GLCT:c.347+4C>T (chr13-31247103-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_194318.4(B3GLCT):c.347+4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,607,250 control chromosomes in the GnomAD database, including 98,488 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10798 hom., cov: 29)

Exomes 𝑓: 0.33 ( 87690 hom. )

Consequence

B3GLCT
NM_194318.4 splice_region, intron

Scores

Splicing: ADA: 0.0001060

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0350

Publications

31 publications found

Variant links:

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), G2P, Genomics England PanelApp, Orphanet

B3GLCT links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 13-31247103-C-T is Benign according to our data. Variant chr13-31247103-C-T is described in ClinVar as Benign. ClinVar VariationId is 96627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194318.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GLCT	NM_194318.4	MANE Select	c.347+4C>T		splice_region intron	N/A	NP_919299.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
B3GLCT	ENST00000343307.5	TSL:1 MANE Select	c.347+4C>T	splice_region intron	N/A	ENSP00000343002.4	Q6Y288
B3GLCT	ENST00000873566.1		c.271-13843C>T	intron	N/A	ENSP00000543625.1
B3GLCT	ENST00000946543.1		c.121-13843C>T	intron	N/A	ENSP00000616602.1

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55089

AN:

151710

Hom.:

10777

Cov.:

show subpopulations

Gnomad AFR

AF:

0.399

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.447

Gnomad ASJ

AF:

0.476

Gnomad EAS

AF:

0.724

Gnomad SAS

AF:

0.500

Gnomad FIN

AF:

0.299

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.371

GnomAD2 exomes

AF:

0.404

AC:

101516

AN:

251078

AF XY:

0.399

show subpopulations

Gnomad AFR exome

AF:

0.396

Gnomad AMR exome

AF:

0.560

Gnomad ASJ exome

AF:

0.461

Gnomad EAS exome

AF:

0.742

Gnomad FIN exome

AF:

0.307

Gnomad NFE exome

AF:

0.296

Gnomad OTH exome

AF:

0.374

GnomAD4 exome

AF:

0.331

AC:

482289

AN:

1455422

Hom.:

87690

Cov.:

AF XY:

0.336

AC XY:

243137

AN XY:

724420

show subpopulations

African (AFR)

AF:

0.399

AC:

13283

AN:

33288

American (AMR)

AF:

0.551

AC:

24613

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.469

AC:

12236

AN:

26070

East Asian (EAS)

AF:

0.723

AC:

28695

AN:

39676

South Asian (SAS)

AF:

0.482

AC:

41498

AN:

86084

European-Finnish (FIN)

AF:

0.301

AC:

16052

AN:

53354

Middle Eastern (MID)

AF:

0.320

AC:

1842

AN:

5756

European-Non Finnish (NFE)

AF:

0.291

AC:

322474

AN:

1106350

Other (OTH)

AF:

0.359

AC:

21596

AN:

60158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

13531

27062

40594

54125

67656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11062

22124

33186

44248

55310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.363

AC:

55145

AN:

151828

Hom.:

10798

Cov.:

AF XY:

0.370

AC XY:

27440

AN XY:

74160

show subpopulations

African (AFR)

AF:

0.399

AC:

16536

AN:

41432

American (AMR)

AF:

0.448

AC:

6844

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.476

AC:

1654

AN:

3472

East Asian (EAS)

AF:

0.724

AC:

3735

AN:

5158

South Asian (SAS)

AF:

0.499

AC:

2396

AN:

4804

European-Finnish (FIN)

AF:

0.299

AC:

3139

AN:

10494

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.291

AC:

19740

AN:

67888

Other (OTH)

AF:

0.374

AC:

790

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1688

3376

5063

6751

8439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.324

Hom.:

3594

Bravo

AF:

0.379

Asia WGS

AF:

0.609

AC:

2113

AN:

3478

EpiCase

AF:

0.296

EpiControl

AF:

0.305

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Peters plus syndrome (3)

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

3.8

(source)

DANN

Benign

0.83

PhyloP100

0.035

Mutation Taster

=86/14

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.016

SpliceAI score (max)

0.36

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.36

Position offset: -4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over