13-31215032-CTTTTTT-CTTTT

Variant names:

• chr13-31215032-CTT-C
• rs398022187
• NM_194318.4:c.71-6_71-5delTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_194318.4(B3GLCT):​c.71-6_71-5delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.066 in 1,071,834 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.076 (0 hom.)
• Consequence: B3GLCT NM_194318.4 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.772
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Variant has high frequency in the AMR (0.121) population. However there is too low homozygotes in high coverage region: (expected more than 1168, got 0).
• BP6: Variant 13-31215032-CTT-C is Benign according to our data. Variant chr13-31215032-CTT-C is described in ClinVar as Benign. ClinVar VariationId is 1227558.Status of the report is criteria_provided_single_submitter, 1 stars.

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.71-6_71-5delTT		splice_region 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.71-18_71-17delTT		intron	N/A	ENSP00000343002.4	Q6Y288
	B3GLCT	ENST00000873566.1		c.71-18_71-17delTT		intron	N/A	ENSP00000543625.1
	B3GLCT	ENST00000946543.1		c.71-18_71-17delTT		intron	N/A	ENSP00000616602.1

Frequencies

GnomAD3 genomes AF: 0.00146 AC: 213 AN: 145804 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00116

Gnomad ASJ AF: 0.000589

Gnomad EAS AF: 0.000398

Gnomad SAS AF: 0.000217

Gnomad FIN AF: 0.00540

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000636

Gnomad OTH AF: 0.00150

GnomAD2 exomes AF: 0.144 AC: 18801 AN: 130932 AF XY: 0.148

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.133

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.128

GnomAD4 exome AF: 0.0762 AC: 70563 AN: 925962 Hom.: 0 AF XY: 0.0774 AC XY: 35549 AN XY: 459514

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0605 AC: 1391 AN: 22996

American (AMR) AF: 0.124 AC: 3366 AN: 27110

Ashkenazi Jewish (ASJ) AF: 0.0950 AC: 1559 AN: 16402

East Asian (EAS) AF: 0.0853 AC: 2062 AN: 24172

South Asian (SAS) AF: 0.0929 AC: 5033 AN: 54170

European-Finnish (FIN) AF: 0.109 AC: 3091 AN: 28462

Middle Eastern (MID) AF: 0.0611 AC: 236 AN: 3862

European-Non Finnish (NFE) AF: 0.0716 AC: 50872 AN: 710266

Other (OTH) AF: 0.0767 AC: 2953 AN: 38522

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00148 AC: 216 AN: 145872 Hom.: 0 Cov.: 0 AF XY: 0.00171 AC XY: 121 AN XY: 70746

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00245 AC: 98 AN: 40038

American (AMR) AF: 0.00116 AC: 17 AN: 14686

Ashkenazi Jewish (ASJ) AF: 0.000589 AC: 2 AN: 3396

East Asian (EAS) AF: 0.000599 AC: 3 AN: 5008

South Asian (SAS) AF: 0.000654 AC: 3 AN: 4586

European-Finnish (FIN) AF: 0.00540 AC: 48 AN: 8884

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.000636 AC: 42 AN: 66070

Other (OTH) AF: 0.00149 AC: 3 AN: 2018

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.101 Hom.: 2424

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.77
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: rs398022187; hg19: chr13-31789169;