16-74472549-G-C

Variant names:

• chr16-74472549-G-C
• rs8059315
• NM_001145667.2:c.2053-138C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145667.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLG1	NM_001145667.2	MANE Select	c.2053-138C>G		intron	N/A	NP_001139139.1
	GLG1	NR_027264.2		n.2158C>G		non_coding_transcript_exon	Exon 14 of 27
	GLG1	NM_012201.6		c.2053-138C>G		intron	N/A	NP_036333.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLG1	ENST00000422840.7	TSL:1 MANE Select	c.2053-138C>G		intron	N/A	ENSP00000405984.3
	GLG1	ENST00000205061.9	TSL:1	c.2053-138C>G		intron	N/A	ENSP00000205061.5
	GLG1	ENST00000567951.5	TSL:1	n.*132-138C>G		intron	N/A	ENSP00000455950.1

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

GnomAD2 exomes AF: 0.151 AC: 20304 AN: 134098 AF XY: 0.152

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

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

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

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: 73 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: 66 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13640 AN: 67974

Other (OTH) AF: 0.160 AC: 338 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.47
PhyloP100		0.023
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8059315; hg19: chr16-74506447;