chr12-75410455-C-T

Variant names:

• chr12-75410455-C-T
• rs142539769
• ENST00000378692.7:c.-66C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000378692.7(GLIPR1L2):​c.-66C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000771 in 1,594,382 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000076 (0 hom.)
• Consequence: GLIPR1L2 ENST00000378692.7 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.469
• Publications: 1 publications found

Genes affected

GLIPR1L2 (HGNC:28592): (GLIPR1 like 2) This gene encodes a member of the cysteine-rich secretory protein, antigen 5, and pathogenesis-related 1 superfamily. Members of this family have roles in a variety of processes, including cancer and immune defense. This gene is located in a cluster with two related genes on chromosome 12. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000378692.7. 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
	GLIPR1L2	NM_001270396.2	MANE Select	c.256C>T	p.Arg86Trp	missense	Exon 2 of 6	NP_001257325.1	Q4G1C9-1
	GLIPR1L2	NM_152436.3		c.256C>T	p.Arg86Trp	missense	Exon 2 of 4	NP_689649.1	Q4G1C9-2
	GLIPR1L2	NR_072995.2		n.414C>T		non_coding_transcript_exon	Exon 3 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLIPR1L2	ENST00000378692.7	TSL:1	c.-66C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 7	ENSP00000367963.3	Q4G1C9-5
	GLIPR1L2	ENST00000550916.6	TSL:1 MANE Select	c.256C>T	p.Arg86Trp	missense	Exon 2 of 6	ENSP00000448248.1	Q4G1C9-1
	GLIPR1L2	ENST00000320460.8	TSL:1	c.256C>T	p.Arg86Trp	missense	Exon 2 of 4	ENSP00000317385.4	Q4G1C9-2

Frequencies

GnomAD3 genomes AF: 0.0000857 AC: 13 AN: 151714 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

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: 0.000133

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000537 AC: 13 AN: 242048 AF XY: 0.0000532

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000619

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000112

Gnomad FIN exome AF: 0.0000470

Gnomad NFE exome AF: 0.0000724

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000762 AC: 110 AN: 1442668 Hom.: 0 Cov.: 30 AF XY: 0.0000725 AC XY: 52 AN XY: 716836

African (AFR) AF: 0.0000305 AC: 1 AN: 32824

American (AMR) AF: 0.0000945 AC: 4 AN: 42328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25550

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39036

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83296

European-Finnish (FIN) AF: 0.0000568 AC: 3 AN: 52856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.0000853 AC: 94 AN: 1101650

Other (OTH) AF: 0.000101 AC: 6 AN: 59446

GnomAD4 genome AF: 0.0000857 AC: 13 AN: 151714 Hom.: 0 Cov.: 32 AF XY: 0.0000675 AC XY: 5 AN XY: 74094

African (AFR) AF: 0.0000242 AC: 1 AN: 41352

American (AMR) AF: 0.000197 AC: 3 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000133 AC: 9 AN: 67794

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000132 Hom.: 0

Bravo AF: 0.000128

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000577 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		0.47
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.18
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.52
MVP		0.50
MPC		0.30
ClinPred		0.75	D
GERP RS		1.8
Varity_R		0.38
gMVP		0.68
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs142539769; hg19: chr12-75804235;