Variant 1-167546113-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_003851.3(CREG1):c.647A>T(p.Asn216Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000413 in 1,602,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

CREG1
NM_003851.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.501

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 Uncertain_significance. Variant got 2 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity CREG1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13217348).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREG1	NM_003851.3 linkuse as main transcript	c.647A>T	p.Asn216Ile	missense_variant	3/4	ENST00000370509.5	NP_003842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREG1	ENST00000370509.5 linkuse as main transcript	c.647A>T	p.Asn216Ile	missense_variant	3/4	1	NM_003851.3	ENSP00000359540	P1
CREG1	ENST00000466652.2 linkuse as main transcript	c.647A>T	p.Asn216Ile	missense_variant	3/5	3		ENSP00000496871

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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:

0.000515

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000236

AC:

AN:

241318

Hom.:

AF XY:

0.000222

AC XY:

AN XY:

130788

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.000313

Gnomad ASJ exome

AF:

0.000106

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000399

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000423

AC:

613

AN:

1450342

Hom.:

Cov.:

AF XY:

0.000388

AC XY:

280

AN XY:

721128

show subpopulations

Gnomad4 AFR exome

AF:

0.0000608

Gnomad4 AMR exome

AF:

0.000402

Gnomad4 ASJ exome

AF:

0.0000391

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.000508

Gnomad4 OTH exome

AF:

0.000468

GnomAD4 genome

AF:

0.000322

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000396

Hom.:

Bravo

AF:

0.000461

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000181

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

Mar 07, 2024

The c.647A>T (p.N216I) alteration is located in exon 3 (coding exon 3) of the CREG1 gene. This alteration results from a A to T substitution at nucleotide position 647, causing the asparagine (N) at amino acid position 216 to be replaced by an isoleucine (I). 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

Uncertain

0.41

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

.;T

Eigen

Benign

0.091

Eigen_PC

Benign

-0.027

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.7

.;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-5.2

.;D

REVEL

Benign

0.14

Sift

Uncertain

0.017

.;D

Sift4G

Uncertain

0.016

.;D

Polyphen

0.97

.;D

Vest4

0.48

MVP

0.43

MPC

0.40

ClinPred

0.40

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.43

gMVP

0.46

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