chr16-5071691-C-A

Variant names:

• chr16-5071691-C-A
• rs17523310
• ENST00000588623.5:c.-125-1260C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.442
• Publications: 2 publications found

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]

ALG1 Gene-Disease associations (from GenCC):

• ALG1-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, PanelApp Australia, G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1294322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000588623.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG1	NM_019109.5	MANE Select	c.-159C>A		upstream_gene	N/A	NP_061982.3
	ALG1	NM_001438123.1		c.-159C>A		upstream_gene	N/A	NP_001425052.1	A0A804HJL6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG1	ENST00000588623.5	TSL:1	c.-125-1260C>A		intron	N/A	ENSP00000468118.1	Q9BT22-2
	ALG1	ENST00000682985.1		c.-99-3697C>A		intron	N/A	ENSP00000507598.1	A0A804HJQ1
	ALG1	ENST00000682327.1		c.-99-3697C>A		intron	N/A	ENSP00000507058.1	A0A804HIG6

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

African (AFR) AF: 0.0407 AC: 1030 AN: 25278

American (AMR) AF: 0.145 AC: 4551 AN: 31300

Ashkenazi Jewish (ASJ) AF: 0.0981 AC: 2027 AN: 20658

East Asian (EAS) AF: 0.124 AC: 4246 AN: 34258

South Asian (SAS) AF: 0.128 AC: 8579 AN: 67022

European-Finnish (FIN) AF: 0.0858 AC: 2751 AN: 32048

Middle Eastern (MID) AF: 0.105 AC: 354 AN: 3358

European-Non Finnish (NFE) AF: 0.0885 AC: 71925 AN: 812340

Other (OTH) AF: 0.0899 AC: 4241 AN: 47168

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

African (AFR) AF: 0.0474 AC: 1971 AN: 41562

American (AMR) AF: 0.131 AC: 2003 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0971 AC: 337 AN: 3470

East Asian (EAS) AF: 0.109 AC: 562 AN: 5166

South Asian (SAS) AF: 0.129 AC: 625 AN: 4832

European-Finnish (FIN) AF: 0.0779 AC: 827 AN: 10616

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0884 AC: 6011 AN: 68022

Other (OTH) AF: 0.0833 AC: 176 AN: 2112

Alfa AF: 0.0841 Hom.: 92

Bravo AF: 0.0841

Asia WGS AF: 0.121 AC: 421 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.8
DANN	Benign	0.45
PhyloP100		0.44
PromoterAI		0.037	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs17523310; hg19: chr16-5121692; COSMIC: COSV107273972; COSMIC: COSV107273972;