Variant chr6-44392796-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_001253.4(CDC5L):c.279G>A(p.Ala93=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 1,613,848 control chromosomes in the GnomAD database, including 2,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.049 ( 354 hom., cov: 33)

Exomes 𝑓: 0.035 ( 1817 hom. )

Consequence

CDC5L
NM_001253.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.251

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 6-44392796-G-A is Benign according to our data. Variant chr6-44392796-G-A is described in ClinVar as [Benign]. Clinvar id is 1282740.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.251 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC5L	NM_001253.4 linkuse as main transcript	c.279G>A	p.Ala93=	synonymous_variant	3/16	ENST00000371477.4	NP_001244.1
POLR1C	NM_001318876.2 linkuse as main transcript	c.946-49094G>A		intron_variant			NP_001305805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC5L	ENST00000371477.4 linkuse as main transcript	c.279G>A	p.Ala93=	synonymous_variant	3/16	1	NM_001253.4	ENSP00000360532	P1

Frequencies

GnomAD3 genomes

AF:

0.0487

AC:

7414

AN:

152102

Hom.:

348

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0316

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.0929

Gnomad SAS

AF:

0.0493

Gnomad FIN

AF:

0.0970

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0245

Gnomad OTH

AF:

0.0544

GnomAD3 exomes

AF:

0.0620

AC:

15580

AN:

251406

Hom.:

973

AF XY:

0.0575

AC XY:

7807

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.0320

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.0170

Gnomad EAS exome

AF:

0.0913

Gnomad SAS exome

AF:

0.0505

Gnomad FIN exome

AF:

0.0906

Gnomad NFE exome

AF:

0.0245

Gnomad OTH exome

AF:

0.0525

GnomAD4 exome

AF:

0.0349

AC:

51028

AN:

1461628

Hom.:

1817

Cov.:

AF XY:

0.0350

AC XY:

25478

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.0327

Gnomad4 AMR exome

AF:

0.185

Gnomad4 ASJ exome

AF:

0.0163

Gnomad4 EAS exome

AF:

0.103

Gnomad4 SAS exome

AF:

0.0512

Gnomad4 FIN exome

AF:

0.0846

Gnomad4 NFE exome

AF:

0.0232

Gnomad4 OTH exome

AF:

0.0360

GnomAD4 genome

AF:

0.0488

AC:

7433

AN:

152220

Hom.:

354

Cov.:

AF XY:

0.0554

AC XY:

4122

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0315

Gnomad4 AMR

AF:

0.165

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.0927

Gnomad4 SAS

AF:

0.0495

Gnomad4 FIN

AF:

0.0970

Gnomad4 NFE

AF:

0.0245

Gnomad4 OTH

AF:

0.0539

Alfa

AF:

0.0329

Hom.:

149

Bravo

AF:

0.0538

Asia WGS

AF:

0.0690

AC:

239

AN:

3478

EpiCase

AF:

0.0266

EpiControl

AF:

0.0307

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

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

6.8

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

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