rs4657669

Positions:

• chr1-167552188-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003851.3(CREG1):​c.354+1200G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0803 in 152,202 control chromosomes in the GnomAD database, including 701 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.080 (701 hom., cov: 33)
• Consequence: CREG1 NM_003851.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREG1	NM_003851.3	c.354+1200G>A		intron_variant		ENST00000370509.5	NP_003842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREG1	ENST00000370509.5	c.354+1200G>A		intron_variant		1	NM_003851.3	ENSP00000359540	P1
CREG1	ENST00000466652.2	c.354+1200G>A		intron_variant		3		ENSP00000496871

Frequencies

GnomAD3 genomes AF: 0.0805 AC: 12239 AN: 152084 Hom.: 705 Cov.: 33

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0969

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.0978

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0847

Gnomad OTH AF: 0.0967

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0803 AC: 12221 AN: 152202 Hom.: 701 Cov.: 33 AF XY: 0.0853 AC XY: 6344 AN XY: 74408

Gnomad4 AFR AF: 0.0185

Gnomad4 AMR AF: 0.0967

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.0968

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.0847

Gnomad4 OTH AF: 0.0961

Alfa AF: 0.0850 Hom.: 522

Bravo AF: 0.0757

Asia WGS AF: 0.142 AC: 494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.7
DANN	Benign	0.86

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

Other links and lift over

dbSNP: rs4657669; hg19: chr1-167521425;