rs1783515

Positions:

• chr11-78109624-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024079.5(ALG8):​c.899-43A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,536,924 control chromosomes in the GnomAD database, including 26,485 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4395 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22090 hom.)
• Consequence: ALG8 NM_024079.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.261

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-78109624-T-C is Benign according to our data. Variant chr11-78109624-T-C is described in ClinVar as [Benign]. Clinvar id is 261683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG8	NM_024079.5	c.899-43A>G		intron_variant		ENST00000299626.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG8	ENST00000299626.10	c.899-43A>G		intron_variant		1	NM_024079.5	P3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33048 AN: 151832 Hom.: 4392 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.0976

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.203

GnomAD3 exomes AF: 0.181 AC: 43439 AN: 240636 Hom.: 4506 AF XY: 0.180 AC XY: 23497 AN XY: 130372

Gnomad AFR exome AF: 0.389

Gnomad AMR exome AF: 0.0937

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.301

Gnomad SAS exome AF: 0.219

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.172 AC: 237733 AN: 1384976 Hom.: 22090 Cov.: 24 AF XY: 0.172 AC XY: 118929 AN XY: 693092

Gnomad4 AFR exome AF: 0.397

Gnomad4 AMR exome AF: 0.0980

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.218 AC: 33071 AN: 151948 Hom.: 4395 Cov.: 32 AF XY: 0.212 AC XY: 15780 AN XY: 74282

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.0976

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.201

Alfa AF: 0.187 Hom.: 569

Bravo AF: 0.229

Asia WGS AF: 0.226 AC: 786 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs1783515; hg19: chr11-77820670;