6-44387962-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001253.4(CDC5L):c.45+94T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 1,220,142 control chromosomes in the GnomAD database, including 398,517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (41640 hom., cov: 32)
  • Exomes 𝑓: 0.81 (356877 hom.)
• Consequence: CDC5L NM_001253.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.55

Genes affected

CDC5L (HGNC:1743): (cell division cycle 5 like) The protein encoded by this gene shares a significant similarity with Schizosaccharomyces pombe cdc5 gene product, which is a cell cycle regulator important for G2/M transition. This protein has been demonstrated to act as a positive regulator of cell cycle G2/M progression. It was also found to be an essential component of a non-snRNA spliceosome, which contains at least five additional protein factors and is required for the second catalytic step of pre-mRNA splicing. [provided by RefSeq, Jul 2008]

POLR1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 6-44387962-T-C is Benign according to our data. Variant chr6-44387962-T-C is described in ClinVar as [Benign]. Clinvar id is 1273866.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC5L	NM_001253.4	c.45+94T>C		intron_variant		ENST00000371477.4
POLR1C	NM_001318876.2	c.946-53928T>C		intron_variant
LOC124901323	XR_007059595.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC5L	ENST00000371477.4	c.45+94T>C		intron_variant		1	NM_001253.4	P1

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109856 AN: 152048 Hom.: 41635 Cov.: 32

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.739

GnomAD4 exome AF: 0.806 AC: 861105 AN: 1067976 Hom.: 356877 AF XY: 0.800 AC XY: 432433 AN XY: 540546

Gnomad4 AFR exome AF: 0.558

Gnomad4 AMR exome AF: 0.664

Gnomad4 ASJ exome AF: 0.835

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.597

Gnomad4 FIN exome AF: 0.791

Gnomad4 NFE exome AF: 0.864

Gnomad4 OTH exome AF: 0.767

GnomAD4 genome AF: 0.722 AC: 109887 AN: 152166 Hom.: 41640 Cov.: 32 AF XY: 0.710 AC XY: 52820 AN XY: 74390

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.831

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.863

Gnomad4 OTH AF: 0.737

Alfa AF: 0.791 Hom.: 6015

Bravo AF: 0.708

Asia WGS AF: 0.387 AC: 1350 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.13
Dann	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs2297331; hg19: chr6-44355699; COSMIC: COSV65176302;