14-105010321-T-C

Position:

• chr14-105010321-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDCA4	NM_017955.4	c.*883A>G		3_prime_UTR_variant	2/2	ENST00000336219.4
CDCA4	NM_145701.4	c.*357A>G		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDCA4	ENST00000336219.4	c.*883A>G		3_prime_UTR_variant	2/2	1	NM_017955.4	P1
CDCA4	ENST00000392590.3	c.*357A>G		3_prime_UTR_variant	3/3	1		P1
CLBA1	ENST00000548178.1	n.304T>C		non_coding_transcript_exon_variant	3/3	3

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

Gnomad4 FIN exome AF: 0.816

Gnomad4 NFE exome AF: 0.917

Gnomad4 OTH exome AF: 1.00

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

Gnomad4 AFR AF: 0.782

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.805

Gnomad4 NFE AF: 0.808

Gnomad4 OTH AF: 0.791

Alfa AF: 0.802 Hom.: 30093

Bravo AF: 0.786

Asia WGS AF: 0.601 AC: 2096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.61
DANN	Benign	0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3204173; hg19: chr14-105476658;