1-167544411-G-C

Variant names:

• chr1-167544411-G-C
• rs16859185
• NM_003851.3:c.659+1690C>G

Variant summary

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

The ENST00000370509.5(CREG1):​c.659+1690C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 151,910 control chromosomes in the GnomAD database, including 2,981 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 0.19 (2981 hom., cov: 31)
• Consequence: CREG1 ENST00000370509.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000370509.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREG1	NM_003851.3	MANE Select	c.659+1690C>G		intron	N/A	NP_003842.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREG1	ENST00000370509.5	TSL:1 MANE Select	c.659+1690C>G		intron	N/A	ENSP00000359540.4
	CREG1	ENST00000466652.2	TSL:3	c.659+1690C>G		intron	N/A	ENSP00000496871.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28567 AN: 151790 Hom.: 2984 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.188 AC: 28563 AN: 151910 Hom.: 2981 Cov.: 31 AF XY: 0.191 AC XY: 14207 AN XY: 74218

African (AFR) AF: 0.101 AC: 4200 AN: 41452

American (AMR) AF: 0.270 AC: 4109 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 815 AN: 3464

East Asian (EAS) AF: 0.309 AC: 1596 AN: 5166

South Asian (SAS) AF: 0.165 AC: 796 AN: 4814

European-Finnish (FIN) AF: 0.240 AC: 2516 AN: 10492

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13930 AN: 67964

Other (OTH) AF: 0.196 AC: 413 AN: 2112

Alfa AF: 0.100 Hom.: 138

Bravo AF: 0.194

Asia WGS AF: 0.212 AC: 737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.50
PhyloP100		-1.9
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: rs16859185; hg19: chr1-167513648;