Variant 6-44387945-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001253.4(CDC5L):c.45+77G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 1,449,918 control chromosomes in the GnomAD database, including 481,075 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.72 ( 41449 hom., cov: 32)

Exomes 𝑓: 0.81 ( 439626 hom. )

Consequence

CDC5L
NM_001253.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0630

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:

POLR1C (HGNC:):

POLR1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 6-44387945-G-A is Benign according to our data. Variant chr6-44387945-G-A is described in ClinVar as [Benign]. Clinvar id is 1240804.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	Effect	MANE	Protein
CDC5L	NM_001253.4 linkuse as main transcript	c.45+77G>A	intron_variant	ENST00000371477.4	NP_001244.1
POLR1C	NM_001318876.2 linkuse as main transcript	c.946-53945G>A	intron_variant		NP_001305805.1
LOC124901323	XR_007059595.1 linkuse as main transcript		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC5L	ENST00000371477.4 linkuse as main transcript	c.45+77G>A		intron_variant		1	NM_001253.4	ENSP00000360532	P1

Frequencies

GnomAD3 genomes

AF:

0.721

AC:

109506

AN:

151904

Hom.:

41444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.559

Gnomad AMI

AF:

0.887

Gnomad AMR

AF:

0.664

Gnomad ASJ

AF:

0.831

Gnomad EAS

AF:

0.258

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.774

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.863

Gnomad OTH

AF:

0.738

GnomAD4 exome

AF:

0.813

AC:

1055297

AN:

1297896

Hom.:

439626

AF XY:

0.807

AC XY:

520772

AN XY:

645092

show subpopulations

Gnomad4 AFR exome

AF:

0.550

Gnomad4 AMR exome

AF:

0.661

Gnomad4 ASJ exome

AF:

0.835

Gnomad4 EAS exome

AF:

0.281

Gnomad4 SAS exome

AF:

0.596

Gnomad4 FIN exome

AF:

0.786

Gnomad4 NFE exome

AF:

0.865

Gnomad4 OTH exome

AF:

0.769

GnomAD4 genome

AF:

0.721

AC:

109536

AN:

152022

Hom.:

41449

Cov.:

AF XY:

0.708

AC XY:

52625

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.558

Gnomad4 AMR

AF:

0.663

Gnomad4 ASJ

AF:

0.831

Gnomad4 EAS

AF:

0.258

Gnomad4 SAS

AF:

0.554

Gnomad4 FIN

AF:

0.774

Gnomad4 NFE

AF:

0.862

Gnomad4 OTH

AF:

0.735

Alfa

AF:

0.758

Hom.:

2843

Bravo

AF:

0.706

Asia WGS

AF:

0.386

AC:

1346

AN:

3476

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

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.7

DANN

Benign

0.92

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

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