Variant 12-75490478-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006851.3(GLIPR1):c.493C>G(p.Leu165Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,451,820 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000083 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

GLIPR1
NM_006851.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.72

Variant links:

Genes affected

GLIPR1 (HGNC:17001): (GLI pathogenesis related 1) This gene encodes a protein with similarity to both the pathogenesis-related protein (PR) superfamily and the cysteine-rich secretory protein (CRISP) family. Increased expression of this gene is associated with myelomocytic differentiation in macrophage and decreased expression of this gene through gene methylation is associated with prostate cancer. The protein has proapoptotic activities in prostate and bladder cancer cells. This gene is a member of a cluster on chromosome 12 containing two other similar genes. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

GLIPR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0394471).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLIPR1	NM_006851.3 linkuse as main transcript	c.493C>G	p.Leu165Val	missense_variant	3/6	ENST00000266659.8	NP_006842.2	P48060-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GLIPR1	ENST00000266659.8 linkuse as main transcript	c.493C>G	p.Leu165Val	missense_variant	3/6	1	NM_006851.3	ENSP00000266659.3	P48060-1
GLIPR1	ENST00000456650.7 linkuse as main transcript	c.564C>G	p.Leu188Leu	synonymous_variant	4/6	1		ENSP00000391144.3	F6VVE8
GLIPR1	ENST00000550491.1 linkuse as main transcript	c.141C>G	p.Leu47Leu	synonymous_variant	3/4	3		ENSP00000448008.1	J3QTC9
GLIPR1	ENST00000536703.5 linkuse as main transcript	n.421-5099C>G		intron_variant		2		ENSP00000440595.1	B4E3S5

Frequencies

GnomAD3 genomes

AF:

0.0000829

AC:

AN:

132644

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000223

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000882

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:

0.0000310

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251094

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000129

AC:

AN:

1319046

Hom.:

Cov.:

AF XY:

0.0000107

AC XY:

AN XY:

655956

show subpopulations

Gnomad4 AFR exome

AF:

0.000203

Gnomad4 AMR exome

AF:

0.0000991

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000494

Gnomad4 NFE exome

AF:

9.81e-7

Gnomad4 OTH exome

AF:

0.0000783

GnomAD4 genome

AF:

0.0000828

AC:

AN:

132774

Hom.:

Cov.:

AF XY:

0.0000478

AC XY:

AN XY:

62702

show subpopulations

Gnomad4 AFR

AF:

0.000222

Gnomad4 AMR

AF:

0.0000881

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000310

Gnomad4 OTH

AF:

0.00

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

The c.493C>G (p.L165V) alteration is located in exon 3 (coding exon 3) of the GLIPR1 gene. This alteration results from a C to G substitution at nucleotide position 493, causing the leucine (L) at amino acid position 165 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.38

DANN

Benign

0.94

DEOGEN2

Benign

0.070

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.42

M_CAP

Benign

0.0096

MetaRNN

Benign

0.039

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.83

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.32

REVEL

Benign

0.038

Sift

Benign

0.28

Sift4G

Benign

0.13

Polyphen

0.028

Vest4

0.078

MVP

0.30

MPC

0.15

ClinPred

0.017

GERP RS

-4.6

Varity_R

0.038

gMVP

0.45

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over