dbSNP rs8059315: GLG1:c.2053-138C>G (chr16-74472549-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001145667.2(GLG1):c.2053-138C>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 1,466,034 control chromosomes in the GnomAD database, including 24,500 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2330 hom., cov: 33)

Exomes 𝑓: 0.18 ( 22170 hom. )

Consequence

GLG1
NM_001145667.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0230

Publications

11 publications found

Variant links:

Genes affected

GLG1 (HGNC:4316): (golgi glycoprotein 1) Predicted to enable fibroblast growth factor binding activity. Predicted to act upstream of or within several processes, including negative regulation of protein processing; negative regulation of transforming growth factor beta receptor signaling pathway; and regulation of chondrocyte differentiation. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

GLG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLG1	NM_001145667.2 link	c.2053-138C>G		intron_variant	Intron 13 of 25	ENST00000422840.7	NP_001139139.1	Q92896-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLG1	ENST00000422840.7 link	c.2053-138C>G		intron_variant	Intron 13 of 25	1	NM_001145667.2	ENSP00000405984.3		Q92896-1

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24963

AN:

152050

Hom.:

2330

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.178

Gnomad EAS

AF:

0.0141

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.160

GnomAD2 exomes

AF:

0.151

AC:

20304

AN:

134098

AF XY:

0.152

show subpopulations

Gnomad AFR exome

AF:

0.121

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.172

Gnomad EAS exome

AF:

0.0122

Gnomad FIN exome

AF:

0.239

Gnomad NFE exome

AF:

0.197

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.177

AC:

232974

AN:

1313866

Hom.:

22170

Cov.:

AF XY:

0.176

AC XY:

114958

AN XY:

651630

show subpopulations

African (AFR)

AF:

0.115

AC:

3433

AN:

29820

American (AMR)

AF:

0.116

AC:

3964

AN:

34128

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

4343

AN:

24262

East Asian (EAS)

AF:

0.0159

AC:

553

AN:

34678

South Asian (SAS)

AF:

0.115

AC:

8722

AN:

75726

European-Finnish (FIN)

AF:

0.228

AC:

7684

AN:

33730

Middle Eastern (MID)

AF:

0.238

AC:

1302

AN:

5460

European-Non Finnish (NFE)

AF:

0.189

AC:

193270

AN:

1020964

Other (OTH)

AF:

0.176

AC:

9703

AN:

55098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

7945

15890

23834

31779

39724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6534

13068

19602

26136

32670

<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:

0.164

AC:

24972

AN:

152168

Hom.:

2330

Cov.:

AF XY:

0.164

AC XY:

12174

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.117

AC:

4874

AN:

41532

American (AMR)

AF:

0.133

AC:

2034

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

616

AN:

3470

East Asian (EAS)

AF:

0.0141

AC:

AN:

5178

South Asian (SAS)

AF:

0.115

AC:

554

AN:

4830

European-Finnish (FIN)

AF:

0.237

AC:

2502

AN:

10576

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.201

AC:

13640

AN:

67974

Other (OTH)

AF:

0.160

AC:

338

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1060

2119

3179

4238

5298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

266

532

798

1064

1330

<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:

0.192

Hom.:

571

Bravo

AF:

0.153

Asia WGS

AF:

0.0830

AC:

291

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.6

(source)

DANN

Benign

0.47

PhyloP100

0.023

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over