11-66346115-CTTA-C

Position:

• chr11-66346115-CTTA-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4_Supporting PP5_Moderate

The NM_006876.3(B4GAT1):​c.1179_1181del​(p.Asn393del) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: B4GAT1 NM_006876.3 inframe_deletion
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.11

Genes affected

B4GAT1 (HGNC:15685): (beta-1,4-glucuronyltransferase 1) This gene encodes a member of the beta-1,3-N-acetylglucosaminyltransferase family. This enzyme is a type II transmembrane protein. It is essential for the synthesis of poly-N-acetyllactosamine, a determinant for the blood group i antigen. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_006876.3. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 11-66346115-CTTA-C is Pathogenic according to our data. Variant chr11-66346115-CTTA-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 503771.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B4GAT1	NM_006876.3	c.1179_1181del	p.Asn393del	inframe_deletion	2/2	ENST00000311181.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B4GAT1	ENST00000311181.5	c.1179_1181del	p.Asn393del	inframe_deletion	2/2	1	NM_006876.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

GeneDx

Jul 25, 2017

The c.1177_1179delAAT variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016). The c.1177_1179delAAT variant results in an in-frame deletion of a single Asparagine residue, denoted p.Asn393del. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, other in-frame deletions variants have not been reported in the Human Gene Mutation Database in association with Walker-Warburg syndrome (Stenson et al., 2014). -

Computational scores

Source: dbNSFP v4.3

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: rs1555016276; hg19: chr11-66113586;