1-167553486-C-G

Position:

• chr1-167553486-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003851.3(CREG1):​c.256G>C​(p.Ala86Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000015 in 1,336,392 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: CREG1 NM_003851.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.22

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREG1	NM_003851.3	c.256G>C	p.Ala86Pro	missense_variant	1/4	ENST00000370509.5	NP_003842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREG1	ENST00000370509.5	c.256G>C	p.Ala86Pro	missense_variant	1/4	1	NM_003851.3	ENSP00000359540	P1
CREG1	ENST00000466652.2	c.256G>C	p.Ala86Pro	missense_variant	1/5	3		ENSP00000496871

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000150 AC: 2 AN: 1336392 Hom.: 0 Cov.: 32 AF XY: 0.00000152 AC XY: 1 AN XY: 658518

Gnomad4 AFR exome AF: 0.00

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: 0.00000189

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

The c.256G>C (p.A86P) alteration is located in exon 1 (coding exon 1) of the CREG1 gene. This alteration results from a G to C substitution at nucleotide position 256, causing the alanine (A) at amino acid position 86 to be replaced by a proline (P). 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	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	.;T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.71	T;T
M_CAP	Uncertain	0.28	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Uncertain	2.4	.;M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.6	.;D
REVEL	Uncertain	0.30
Sift	Benign	0.13	.;T
Sift4G	Benign	0.082	.;T
Polyphen		0.71	.;P
Vest4		0.71
MutPred		0.51		Gain of disorder (P = 0.0379);Gain of disorder (P = 0.0379);
MVP		0.38
MPC		0.46
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.90
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-167522723;