rs3767443

Variant names:

• chr1-167551227-T-C
• rs3767443
• NM_003851.3:c.354+2161A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003851.3(CREG1):​c.354+2161A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,092 control chromosomes in the GnomAD database, including 5,316 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 0.25 (5316 hom., cov: 32)
• Consequence: CREG1 NM_003851.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREG1	NM_003851.3	c.354+2161A>G		intron_variant	Intron 1 of 3	ENST00000370509.5	NP_003842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREG1	ENST00000370509.5	c.354+2161A>G		intron_variant	Intron 1 of 3	1	NM_003851.3	ENSP00000359540.4
CREG1	ENST00000466652.2	c.354+2161A>G		intron_variant	Intron 1 of 4	3		ENSP00000496871.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37400 AN: 151974 Hom.: 5309 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.246 AC: 37422 AN: 152092 Hom.: 5316 Cov.: 32 AF XY: 0.249 AC XY: 18542 AN XY: 74338

African (AFR) AF: 0.100 AC: 4158 AN: 41498

American (AMR) AF: 0.265 AC: 4059 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1002 AN: 3470

East Asian (EAS) AF: 0.185 AC: 955 AN: 5168

South Asian (SAS) AF: 0.345 AC: 1665 AN: 4828

European-Finnish (FIN) AF: 0.341 AC: 3598 AN: 10544

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21107 AN: 67972

Other (OTH) AF: 0.256 AC: 541 AN: 2116

Alfa AF: 0.278 Hom.: 13425

Bravo AF: 0.229

Asia WGS AF: 0.246 AC: 858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.64
DANN	Benign	0.52
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3767443; hg19: chr1-167520464;