rs3204173

Variant names:

• chr14-105010321-T-C
• rs3204173
• NM_017955.4:c.*883A>G

Variant summary

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

The NM_017955.4(CDCA4):​c.*883A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 152,554 control chromosomes in the GnomAD database, including 47,575 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 0.79 (47464 hom., cov: 33)
  • Exomes 𝑓: 0.82 (111 hom.)
• Consequence: CDCA4 NM_017955.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 5 publications found

Genes affected

CDCA4 (HGNC:14625): (cell division cycle associated 4) This gene encodes a protein that belongs to the E2F family of transcription factors. This protein regulates E2F-dependent transcriptional activation and cell proliferation, mainly through the E2F/retinoblastoma protein pathway. It also functions in the regulation of JUN oncogene expression. This protein shows distinctive nuclear-mitotic apparatus distribution, it is involved in spindle organization from prometaphase, and may also play a role as a midzone factor involved in chromosome segregation or cytokinesis. Two alternatively spliced transcript variants encoding the same protein have been noted for this gene. Two pseudogenes have also been identified on chromosome 1. [provided by RefSeq, May 2014]

CLBA1 (HGNC:20126): (clathrin binding box of aftiphilin containing 1) Predicted to enable clathrin binding activity. Predicted to be involved in intracellular transport. Predicted to be part of AP-1 adaptor complex. Predicted to be active in trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017955.4. 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
	CDCA4	NM_017955.4	MANE Select	c.*883A>G		3_prime_UTR	Exon 2 of 2	NP_060425.2
	CDCA4	NM_145701.4		c.*357A>G		3_prime_UTR	Exon 3 of 3	NP_663747.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDCA4	ENST00000336219.4	TSL:1 MANE Select	c.*883A>G		3_prime_UTR	Exon 2 of 2	ENSP00000337226.3
	CDCA4	ENST00000392590.3	TSL:1	c.*357A>G		3_prime_UTR	Exon 3 of 3	ENSP00000376369.3
	CDCA4	ENST00000896959.1		c.*883A>G		3_prime_UTR	Exon 3 of 3	ENSP00000567018.1

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119874 AN: 152112 Hom.: 47433 Cov.: 33

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.792

GnomAD4 exome AF: 0.821 AC: 266 AN: 324 Hom.: 111 Cov.: 0 AF XY: 0.785 AC XY: 146 AN XY: 186

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.816 AC: 253 AN: 310

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.917 AC: 11 AN: 12

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.788 AC: 119960 AN: 152230 Hom.: 47464 Cov.: 33 AF XY: 0.786 AC XY: 58530 AN XY: 74434

African (AFR) AF: 0.782 AC: 32479 AN: 41532

American (AMR) AF: 0.796 AC: 12174 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2928 AN: 3468

East Asian (EAS) AF: 0.548 AC: 2840 AN: 5178

South Asian (SAS) AF: 0.711 AC: 3431 AN: 4824

European-Finnish (FIN) AF: 0.805 AC: 8545 AN: 10614

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.808 AC: 54973 AN: 68004

Other (OTH) AF: 0.791 AC: 1671 AN: 2112

Alfa AF: 0.801 Hom.: 41562

Bravo AF: 0.786

Asia WGS AF: 0.601 AC: 2096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.61
DANN	Benign	0.23
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs3204173; hg19: chr14-105476658;