rs8059315

Positions:

• chr16-74472549-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GLG1	NM_001145667.2	c.2053-138C>G		intron_variant		ENST00000422840.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLG1	ENST00000422840.7	c.2053-138C>G		intron_variant		1	NM_001145667.2	P2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24963 AN: 152050 Hom.: 2330 Cov.: 33

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

GnomAD3 exomes AF: 0.151 AC: 20304 AN: 134098 Hom.: 1769 AF XY: 0.152 AC XY: 10986 AN XY: 72044

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 SAS exome AF: 0.119

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.: 19 AF XY: 0.176 AC XY: 114958 AN XY: 651630

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.179

Gnomad4 EAS exome AF: 0.0159

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.176

GnomAD4 genome AF: 0.164 AC: 24972 AN: 152168 Hom.: 2330 Cov.: 33 AF XY: 0.164 AC XY: 12174 AN XY: 74404

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.160

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
DANN	Benign	0.47

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

LitVar

Other links and lift over

dbSNP: rs8059315; hg19: chr16-74506447;