16-5071691-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000588623.5(ALG1):c.-125-1260C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0917 in 1,225,716 control chromosomes in the GnomAD database, including 5,567 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.083 (598 hom., cov: 33)
  • Exomes 𝑓: 0.093 (4969 hom.)
• Consequence: ALG1 ENST00000588623.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.442

Genes affected

ALG1 (HGNC:18294): (ALG1 chitobiosyldiphosphodolichol beta-mannosyltransferase) The enzyme encoded by this gene catalyzes the first mannosylation step in the biosynthesis of lipid-linked oligosaccharides. This gene is mutated in congenital disorder of glycosylation type Ik. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 16-5071691-C-A is Benign according to our data. Variant chr16-5071691-C-A is described in ClinVar as [Benign]. Clinvar id is 1294322.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG1	ENST00000588623.5	c.-125-1260C>A		intron_variant		1
ALG1	ENST00000682020.1	c.-55-5754C>A		intron_variant
ALG1	ENST00000682327.1	c.-99-3697C>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0833 AC: 12673 AN: 152168 Hom.: 596 Cov.: 33

Gnomad AFR AF: 0.0472

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0779

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0884

Gnomad OTH AF: 0.0847

GnomAD4 exome AF: 0.0929 AC: 99704 AN: 1073430 Hom.: 4969 AF XY: 0.0942 AC XY: 50710 AN XY: 538592

Gnomad4 AFR exome AF: 0.0407

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.0981

Gnomad4 EAS exome AF: 0.124

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.0858

Gnomad4 NFE exome AF: 0.0885

Gnomad4 OTH exome AF: 0.0899

GnomAD4 genome AF: 0.0833 AC: 12690 AN: 152286 Hom.: 598 Cov.: 33 AF XY: 0.0830 AC XY: 6181 AN XY: 74462

Gnomad4 AFR AF: 0.0474

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.0971

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0779

Gnomad4 NFE AF: 0.0884

Gnomad4 OTH AF: 0.0833

Alfa AF: 0.0853 Hom.: 89

Bravo AF: 0.0841

Asia WGS AF: 0.121 AC: 421 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	2.8
Dann	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17523310; hg19: chr16-5121692;