rs117111131

Variant names:

• chr13-31247011-T-C
• rs117111131
• NM_194318.4:c.271-12T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_194318.4(B3GLCT):​c.271-12T>C variant causes a 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 NM_194318.4 intron
• Scores: Splicing: ADA: 0.00008837
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.256
• Publications: 3 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), G2P, Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 96625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

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.271-12T>C		intron	N/A	NP_919299.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GLCT	ENST00000343307.5	TSL:1 MANE Select	c.271-12T>C		intron	N/A	ENSP00000343002.4	Q6Y288
	B3GLCT	ENST00000873566.1		c.271-13935T>C		intron	N/A	ENSP00000543625.1
	B3GLCT	ENST00000946543.1		c.121-13935T>C		intron	N/A	ENSP00000616602.1

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

GnomAD2 exomes AF: 0.0214 AC: 5368 AN: 251274 AF XY: 0.0217

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 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

African (AFR) AF: 0.00488 AC: 162 AN: 33182

American (AMR) AF: 0.0176 AC: 786 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.0759 AC: 1977 AN: 26040

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39598

South Asian (SAS) AF: 0.00786 AC: 675 AN: 85924

European-Finnish (FIN) AF: 0.0159 AC: 846 AN: 53316

Middle Eastern (MID) AF: 0.0285 AC: 164 AN: 5748

European-Non Finnish (NFE) AF: 0.0266 AC: 29246 AN: 1098148

Other (OTH) AF: 0.0258 AC: 1546 AN: 59850

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

African (AFR) AF: 0.00524 AC: 216 AN: 41188

American (AMR) AF: 0.0215 AC: 324 AN: 15104

Ashkenazi Jewish (ASJ) AF: 0.0737 AC: 255 AN: 3460

East Asian (EAS) AF: 0.000395 AC: 2 AN: 5064

South Asian (SAS) AF: 0.00527 AC: 25 AN: 4748

European-Finnish (FIN) AF: 0.0123 AC: 128 AN: 10386

Middle Eastern (MID) AF: 0.0240 AC: 7 AN: 292

European-Non Finnish (NFE) AF: 0.0263 AC: 1787 AN: 67856

Other (OTH) AF: 0.0249 AC: 52 AN: 2088

Alfa AF: 0.0274 Hom.: 9

Bravo AF: 0.0199

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Peters plus syndrome (3)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.020
DANN	Benign	0.70
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs117111131; hg19: chr13-31821148;