Variant 1-167553653-C-T 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_003851.3(CREG1):c.89G>A(p.Arg30Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,338,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

CREG1
NM_003851.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.574

Variant links:

Genes affected

CREG1 (HGNC:2351): (cellular repressor of E1A stimulated genes 1) The adenovirus E1A protein both activates and represses gene expression to promote cellular proliferation and inhibit differentiation. The protein encoded by this gene antagonizes transcriptional activation and cellular transformation by E1A. This protein shares limited sequence similarity with E1A and binds both the general transcription factor TBP and the tumor suppressor pRb in vitro. This gene may contribute to the transcriptional control of cell growth and differentiation. [provided by RefSeq, Jul 2008]

CREG1 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=0.03188336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREG1	NM_003851.3 linkuse as main transcript	c.89G>A	p.Arg30Gln	missense_variant	1/4	ENST00000370509.5	NP_003842.1	O75629

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREG1	ENST00000370509.5 linkuse as main transcript	c.89G>A	p.Arg30Gln	missense_variant	1/4	1	NM_003851.3	ENSP00000359540.4		O75629
CREG1	ENST00000466652.2 linkuse as main transcript	c.89G>A	p.Arg30Gln	missense_variant	1/5	3		ENSP00000496871.1		A0A3B3IRL2

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000263

AC:

AN:

11404

Hom.:

AF XY:

0.000276

AC XY:

AN XY:

7248

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000658

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000126

AC:

150

AN:

1186368

Hom.:

Cov.:

AF XY:

0.000137

AC XY:

AN XY:

575296

show subpopulations

Gnomad4 AFR exome

AF:

0.00101

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.0000413

GnomAD4 genome

AF:

0.000460

AC:

AN:

152064

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.00133

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000432

Hom.:

Bravo

AF:

0.000510

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

Apr 07, 2022

The c.89G>A (p.R30Q) alteration is located in exon 1 (coding exon 1) of the CREG1 gene. This alteration results from a G to A substitution at nucleotide position 89, causing the arginine (R) at amino acid position 30 to be replaced by a glutamine (Q). 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

0.13

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

.;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.044

MetaRNN

Benign

0.032

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

.;L

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.090

.;N

REVEL

Benign

0.020

Sift

Benign

0.58

.;T

Sift4G

Benign

0.18

.;T

Polyphen

0.35

.;B

Vest4

0.17

MutPred

0.18

Loss of methylation at R30 (P = 0.0031);Loss of methylation at R30 (P = 0.0031);

MVP

0.11

MPC

0.10

ClinPred

0.064

GERP RS

0.067

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.029

gMVP

0.18

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