11-78100680-T-C

Variant names:

• chr11-78100680-T-C
• rs2845556
• ENST00000679559.1:c.1452+413A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000679559.1(ALG8):​c.1452+413A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,198 control chromosomes in the GnomAD database, including 34,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.67 (34918 hom., cov: 34)
• Consequence: ALG8 ENST00000679559.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.827
• Publications: 7 publications found

Genes affected

ALG8 (HGNC:23161): (ALG8 alpha-1,3-glucosyltransferase) This gene encodes a member of the ALG6/ALG8 glucosyltransferase family. The encoded protein catalyzes the addition of the second glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation of proteins. Mutations in this gene have been associated with congenital disorder of glycosylation type Ih (CDG-Ih). Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ALG8 Gene-Disease associations (from GenCC):

• ALG8-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• polycystic liver disease 3 with or without kidney cysts

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-78100680-T-C is Benign according to our data. Variant chr11-78100680-T-C is described in ClinVar as Benign. ClinVar VariationId is 1224993.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000679559.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG8	ENST00000679559.1		c.1452+413A>G		intron	N/A	ENSP00000505433.1
	ALG8	ENST00000680398.1		c.1452+413A>G		intron	N/A	ENSP00000506189.1

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101623 AN: 152080 Hom.: 34877 Cov.: 34

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.668 AC: 101715 AN: 152198 Hom.: 34918 Cov.: 34 AF XY: 0.665 AC XY: 49461 AN XY: 74408

African (AFR) AF: 0.834 AC: 34626 AN: 41526

American (AMR) AF: 0.522 AC: 7975 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1985 AN: 3470

East Asian (EAS) AF: 0.649 AC: 3363 AN: 5178

South Asian (SAS) AF: 0.618 AC: 2980 AN: 4820

European-Finnish (FIN) AF: 0.646 AC: 6841 AN: 10582

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.616 AC: 41902 AN: 68014

Other (OTH) AF: 0.652 AC: 1379 AN: 2116

Alfa AF: 0.632 Hom.: 5363

Bravo AF: 0.668

Asia WGS AF: 0.658 AC: 2293 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.48
DANN	Benign	0.42
PhyloP100		-0.83

Splicing

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

Other links and lift over

dbSNP: rs2845556; hg19: chr11-77811726;