rs1406

Variant names:

• chr19-29824205-C-A
• rs1406
• NM_001238.4:c.*428C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-29824205-C-A
• chr19-29824205-C-T

Variant summary

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

The NM_001238.4(CCNE1):​c.*428C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 249,640 control chromosomes in the GnomAD database, including 9,380 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 0.28 (6188 hom., cov: 32)
  • Exomes 𝑓: 0.25 (3192 hom.)
• Consequence: CCNE1 NM_001238.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800
• Publications: 23 publications found

Genes affected

CCNE1 (HGNC:1589): (cyclin E1) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK2, whose activity is required for cell cycle G1/S transition. This protein accumulates at the G1-S phase boundary and is degraded as cells progress through S phase. Overexpression of this gene has been observed in many tumors, which results in chromosome instability, and thus may contribute to tumorigenesis. This protein was found to associate with, and be involved in, the phosphorylation of NPAT protein (nuclear protein mapped to the ATM locus), which participates in cell-cycle regulated histone gene expression and plays a critical role in promoting cell-cycle progression in the absence of pRB. [provided by RefSeq, Apr 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNE1	NM_001238.4	c.*428C>A		3_prime_UTR_variant	Exon 12 of 12	ENST00000262643.8	NP_001229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNE1	ENST00000262643.8	c.*428C>A		3_prime_UTR_variant	Exon 12 of 12	1	NM_001238.4	ENSP00000262643.3

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42209 AN: 151890 Hom.: 6172 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.246 AC: 23971 AN: 97632 Hom.: 3192 Cov.: 0 AF XY: 0.243 AC XY: 11214 AN XY: 46084

African (AFR) AF: 0.323 AC: 1409 AN: 4360

American (AMR) AF: 0.345 AC: 1083 AN: 3136

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 896 AN: 5512

East Asian (EAS) AF: 0.394 AC: 4819 AN: 12224

South Asian (SAS) AF: 0.425 AC: 423 AN: 996

European-Finnish (FIN) AF: 0.246 AC: 490 AN: 1990

Middle Eastern (MID) AF: 0.142 AC: 80 AN: 564

European-Non Finnish (NFE) AF: 0.211 AC: 12924 AN: 61152

Other (OTH) AF: 0.240 AC: 1847 AN: 7698

GnomAD4 genome AF: 0.278 AC: 42243 AN: 152008 Hom.: 6188 Cov.: 32 AF XY: 0.284 AC XY: 21095 AN XY: 74288

African (AFR) AF: 0.330 AC: 13684 AN: 41430

American (AMR) AF: 0.346 AC: 5285 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 571 AN: 3472

East Asian (EAS) AF: 0.374 AC: 1929 AN: 5164

South Asian (SAS) AF: 0.415 AC: 2000 AN: 4822

European-Finnish (FIN) AF: 0.251 AC: 2655 AN: 10566

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15212 AN: 67958

Other (OTH) AF: 0.255 AC: 539 AN: 2110

Alfa AF: 0.241 Hom.: 14894

Bravo AF: 0.282

Asia WGS AF: 0.448 AC: 1557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.0
DANN	Benign	0.48
PhyloP100		0.080
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1406; hg19: chr19-30315112;