dbSNP rs17523310: ALG1:c.-125-1260C>A (chr16-5071691-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.442

Publications

2 publications found

Variant links:

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: G2P, Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ALG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	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.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

4967

9934

14901

19868

24835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2478

4956

7434

9912

12390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0833

AC:

12690

AN:

152286

Hom.:

598

Cov.:

AF XY:

0.0830

AC XY:

6181

AN XY:

74462

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0884

AC:

6011

AN:

68022

Other (OTH)

AF:

0.0833

AC:

176

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

590

1180

1769

2359

2949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0841

Hom.:

Bravo

AF:

0.0841

Asia WGS

AF:

0.121

AC:

421

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.8

(source)

DANN

Benign

0.45

PhyloP100

0.44

PromoterAI

0.037

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over