11-134374229-C-G

Position:

• chr11-134374229-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001370461.1(GLB1L2):​c.1680C>G​(p.Thr560=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,611,182 control chromosomes in the GnomAD database, including 41,862 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 0.19 (3391 hom., cov: 33)
  • Exomes 𝑓: 0.22 (38471 hom.)
• Consequence: GLB1L2 NM_001370461.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318

Genes affected

GLB1L2 (HGNC:25129): (galactosidase beta 1 like 2) Predicted to enable beta-galactosidase activity. Predicted to be involved in carbohydrate metabolic process. Predicted to be located in extracellular region. Predicted to be active in vacuole. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=0.318 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLB1L2	NM_001370461.1	c.1680C>G	p.Thr560=	synonymous_variant	17/19	ENST00000535456.7
GLB1L2	NM_001370460.1	c.1842C>G	p.Thr614=	synonymous_variant	18/20
GLB1L2	NM_138342.4	c.1680C>G	p.Thr560=	synonymous_variant	17/20
GLB1L2	XR_007062523.1	n.1754C>G		non_coding_transcript_exon_variant	17/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLB1L2	ENST00000535456.7	c.1680C>G	p.Thr560=	synonymous_variant	17/19	1	NM_001370461.1	P1
GLB1L2	ENST00000529077.5	n.4009C>G		non_coding_transcript_exon_variant	18/22	1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29474 AN: 152042 Hom.: 3390 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.190

GnomAD3 exomes AF: 0.234 AC: 58810 AN: 251422 Hom.: 8252 AF XY: 0.244 AC XY: 33132 AN XY: 135894

Gnomad AFR exome AF: 0.0997

Gnomad AMR exome AF: 0.149

Gnomad ASJ exome AF: 0.211

Gnomad EAS exome AF: 0.506

Gnomad SAS exome AF: 0.368

Gnomad FIN exome AF: 0.230

Gnomad NFE exome AF: 0.202

Gnomad OTH exome AF: 0.221

GnomAD4 exome AF: 0.219 AC: 318829 AN: 1459022 Hom.: 38471 Cov.: 32 AF XY: 0.224 AC XY: 162431 AN XY: 726012

Gnomad4 AFR exome AF: 0.0978

Gnomad4 AMR exome AF: 0.151

Gnomad4 ASJ exome AF: 0.209

Gnomad4 EAS exome AF: 0.514

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.194 AC: 29483 AN: 152160 Hom.: 3391 Cov.: 33 AF XY: 0.202 AC XY: 15011 AN XY: 74394

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.188

Alfa AF: 0.200 Hom.: 698

Bravo AF: 0.180

Asia WGS AF: 0.377 AC: 1306 AN: 3478

EpiCase AF: 0.201

EpiControl AF: 0.207

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3741097; hg19: chr11-134244123; COSMIC: COSV56995234; COSMIC: COSV56995234;