11-134332098-A-G

Variant names:

• chr11-134332098-A-G
• rs114706954
• NM_001370461.1:c.37A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001370461.1(GLB1L2):​c.37A>G​(p.Thr13Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000932 in 1,590,332 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (4 hom., cov: 31)
  • Exomes 𝑓: 0.00048 (4 hom.)
• Consequence: GLB1L2 NM_001370461.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.166
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003944248).
• BP6: Variant 11-134332098-A-G is Benign according to our data. Variant chr11-134332098-A-G is described in ClinVar as Benign. ClinVar VariationId is 717007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00526 (798/151624) while in subpopulation AFR AF = 0.0186 (772/41406). AF 95% confidence interval is 0.0176. There are 4 homozygotes in GnomAd4. There are 365 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370461.1. 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
	GLB1L2	NM_001370461.1	MANE Select	c.37A>G	p.Thr13Ala	missense	Exon 1 of 19	NP_001357390.1	Q8IW92
	GLB1L2	NM_001370460.1		c.37A>G	p.Thr13Ala	missense	Exon 1 of 20	NP_001357389.1
	GLB1L2	NM_138342.4		c.37A>G	p.Thr13Ala	missense	Exon 1 of 20	NP_612351.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLB1L2	ENST00000535456.7	TSL:1 MANE Select	c.37A>G	p.Thr13Ala	missense	Exon 1 of 19	ENSP00000444628.1	Q8IW92
	GLB1L2	ENST00000855671.1		c.37A>G	p.Thr13Ala	missense	Exon 1 of 18	ENSP00000525730.1
	GLB1L2	ENST00000855672.1		c.37A>G	p.Thr13Ala	missense	Exon 1 of 16	ENSP00000525731.1

Frequencies

GnomAD3 genomes AF: 0.00525 AC: 796 AN: 151512 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00288

GnomAD2 exomes AF: 0.00108 AC: 232 AN: 214202 AF XY: 0.000815

Gnomad AFR exome AF: 0.0181

Gnomad AMR exome AF: 0.000386

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000104

Gnomad OTH exome AF: 0.000760

GnomAD4 exome AF: 0.000475 AC: 684 AN: 1438708 Hom.: 4 Cov.: 30 AF XY: 0.000399 AC XY: 285 AN XY: 714294

African (AFR) AF: 0.0189 AC: 603 AN: 31956

American (AMR) AF: 0.000498 AC: 21 AN: 42142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25584

East Asian (EAS) AF: 0.00 AC: 0 AN: 38052

South Asian (SAS) AF: 0.0000483 AC: 4 AN: 82866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4860

European-Non Finnish (NFE) AF: 0.00000272 AC: 3 AN: 1102592

Other (OTH) AF: 0.000892 AC: 53 AN: 59412

GnomAD4 genome AF: 0.00526 AC: 798 AN: 151624 Hom.: 4 Cov.: 31 AF XY: 0.00493 AC XY: 365 AN XY: 74078

African (AFR) AF: 0.0186 AC: 772 AN: 41406

American (AMR) AF: 0.00124 AC: 19 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5034

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67796

Other (OTH) AF: 0.00285 AC: 6 AN: 2104

Alfa AF: 0.00121 Hom.: 1

Bravo AF: 0.00608

ESP6500AA AF: 0.0196 AC: 86

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00138 AC: 166

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	5.9
DANN	Benign	0.62
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	0.77	N
PhyloP100		-0.17
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.36	N
REVEL	Benign	0.18
Sift	Benign	0.29	T
Sift4G	Benign	0.55	T
Polyphen		0.0010	B
Vest4		0.056
MVP		0.20
MPC		0.23
ClinPred		0.0054	T
GERP RS		1.6
PromoterAI		-0.016	Neutral
Varity_R		0.035
gMVP		0.65
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs114706954; hg19: chr11-134201992;