rs3753921

Positions:

• chr1-167543922-T-C

Variant summary

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

The ENST00000370509.5(CREG1):​c.660-1621A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,222 control chromosomes in the GnomAD database, including 6,930 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 0.30 (6930 hom., cov: 33)
• Consequence: CREG1 ENST00000370509.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.99

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREG1	NM_003851.3	c.660-1621A>G		intron_variant		ENST00000370509.5	NP_003842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREG1	ENST00000370509.5	c.660-1621A>G		intron_variant		1	NM_003851.3	ENSP00000359540	P1
CREG1	ENST00000466652.2	c.659+2179A>G		intron_variant		3		ENSP00000496871

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45332 AN: 152104 Hom.: 6917 Cov.: 33

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.298 AC: 45373 AN: 152222 Hom.: 6930 Cov.: 33 AF XY: 0.301 AC XY: 22371 AN XY: 74426

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.289

Alfa AF: 0.308 Hom.: 7843

Bravo AF: 0.289

Asia WGS AF: 0.252 AC: 881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0020
DANN	Benign	0.35

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: rs3753921; hg19: chr1-167513159;