11-78114018-A-G

Variant names:

• chr11-78114018-A-G
• rs572693
• NM_024079.5:c.674-29T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024079.5(ALG8):​c.674-29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,555,466 control chromosomes in the GnomAD database, including 26,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4477 hom., cov: 31)
  • Exomes 𝑓: 0.17 (21619 hom.)
• Consequence: ALG8 NM_024079.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.264
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 11-78114018-A-G is Benign according to our data. Variant chr11-78114018-A-G is described in ClinVar as Benign. ClinVar VariationId is 261682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024079.5. 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
	ALG8	NM_024079.5	MANE Select	c.674-29T>C		intron	N/A	NP_076984.2
	ALG8	NM_001425224.1		c.767-29T>C		intron	N/A	NP_001412153.1
	ALG8	NM_001425225.1		c.674-29T>C		intron	N/A	NP_001412154.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG8	ENST00000299626.10	TSL:1 MANE Select	c.674-29T>C		intron	N/A	ENSP00000299626.5
	ALG8	ENST00000532050.5	TSL:1	n.*58-29T>C		intron	N/A	ENSP00000437199.1
	ALG8	ENST00000679559.1		c.674-29T>C		intron	N/A	ENSP00000505433.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33116 AN: 152000 Hom.: 4471 Cov.: 31

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.0978

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.205

GnomAD2 exomes AF: 0.177 AC: 35128 AN: 197968 AF XY: 0.178

Gnomad AFR exome AF: 0.383

Gnomad AMR exome AF: 0.0963

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.295

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.159

Gnomad OTH exome AF: 0.177

GnomAD4 exome AF: 0.168 AC: 235378 AN: 1403348 Hom.: 21619 Cov.: 28 AF XY: 0.168 AC XY: 116854 AN XY: 696186

African (AFR) AF: 0.393 AC: 12661 AN: 32240

American (AMR) AF: 0.0998 AC: 3863 AN: 38696

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 3900 AN: 25342

East Asian (EAS) AF: 0.295 AC: 11314 AN: 38314

South Asian (SAS) AF: 0.214 AC: 17364 AN: 81112

European-Finnish (FIN) AF: 0.115 AC: 5941 AN: 51498

Middle Eastern (MID) AF: 0.248 AC: 1410 AN: 5684

European-Non Finnish (NFE) AF: 0.157 AC: 167975 AN: 1072002

Other (OTH) AF: 0.187 AC: 10950 AN: 58460

GnomAD4 genome AF: 0.218 AC: 33143 AN: 152118 Hom.: 4477 Cov.: 31 AF XY: 0.213 AC XY: 15860 AN XY: 74396

African (AFR) AF: 0.381 AC: 15781 AN: 41460

American (AMR) AF: 0.130 AC: 1981 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 551 AN: 3472

East Asian (EAS) AF: 0.287 AC: 1480 AN: 5154

South Asian (SAS) AF: 0.205 AC: 990 AN: 4828

European-Finnish (FIN) AF: 0.0978 AC: 1037 AN: 10608

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10674 AN: 67998

Other (OTH) AF: 0.202 AC: 427 AN: 2114

Alfa AF: 0.190 Hom.: 661

Bravo AF: 0.228

Asia WGS AF: 0.225 AC: 785 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

PreventionGenetics, part of Exact Sciences

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	-0.55
CADD	Benign	14
DANN	Benign	0.80
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs572693; hg19: chr11-77825064;