Variant 6-44406319-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001253.4(CDC5L):c.759-4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,595,978 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 8 hom., cov: 32)

Exomes 𝑓: 0.012 ( 123 hom. )

Consequence

CDC5L
NM_001253.4 splice_region, intron

Scores

Splicing: ADA: 0.0005790

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.11

Variant links:

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]

CDC5L links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 6-44406319-A-G is Benign according to our data. Variant chr6-44406319-A-G is described in ClinVar as [Benign]. Clinvar id is 2571251.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1178 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC5L	NM_001253.4 link	c.759-4A>G		splice_region_variant, intron_variant		ENST00000371477.4	NP_001244.1	Q99459
CDC5L	XM_047419605.1 link	c.324-4A>G		splice_region_variant, intron_variant			XP_047275561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC5L	ENST00000371477.4 link	c.759-4A>G		splice_region_variant, intron_variant		1	NM_001253.4	ENSP00000360532.3		Q99459

Frequencies

GnomAD3 genomes

AF:

0.00775

AC:

1179

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00697

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00832

AC:

2022

AN:

243082

Hom.:

AF XY:

0.00851

AC XY:

1117

AN XY:

131318

show subpopulations

Gnomad AFR exome

AF:

0.00226

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.00548

Gnomad EAS exome

AF:

0.0000564

Gnomad SAS exome

AF:

0.00341

Gnomad FIN exome

AF:

0.00771

Gnomad NFE exome

AF:

0.0136

Gnomad OTH exome

AF:

0.0120

GnomAD4 exome

AF:

0.0116

AC:

16680

AN:

1443650

Hom.:

123

Cov.:

AF XY:

0.0113

AC XY:

8132

AN XY:

718522

show subpopulations

Gnomad4 AFR exome

AF:

0.00182

Gnomad4 AMR exome

AF:

0.00312

Gnomad4 ASJ exome

AF:

0.00648

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00319

Gnomad4 FIN exome

AF:

0.00773

Gnomad4 NFE exome

AF:

0.0136

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.00773

AC:

1178

AN:

152328

Hom.:

Cov.:

AF XY:

0.00728

AC XY:

542

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00265

Gnomad4 AMR

AF:

0.00372

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.00697

Gnomad4 NFE

AF:

0.0126

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.0108

Hom.:

Bravo

AF:

0.00732

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.0128

EpiControl

AF:

0.0135

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

CDC5L: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.9

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00058

dbscSNV1_RF

Benign

0.076

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over