Variant 6-44387962-T-C 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+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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.55

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=-0.79).

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	Effect	MANE	Protein
CDC5L	NM_001253.4 linkuse as main transcript	c.45+94T>C	intron_variant	ENST00000371477.4	NP_001244.1
POLR1C	NM_001318876.2 linkuse as main transcript	c.946-53928T>C	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+94T>C		intron_variant		1	NM_001253.4	ENSP00000360532	P1

Frequencies

GnomAD3 genomes

AF:

0.723

AC:

109856

AN:

152048

Hom.:

41635

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.710

AC XY:

52820

AN XY:

74390

show subpopulations

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

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

-0.79

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

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