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6-44392796-G-A

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

2

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.251 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
CDC5LNM_001253.4 linkuse as main transcriptc.279G>A p.Ala93= synonymous_variant 3/16 ENST00000371477.4
POLR1CNM_001318876.2 linkuse as main transcriptc.946-49094G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDC5LENST00000371477.4 linkuse as main transcriptc.279G>A p.Ala93= synonymous_variant 3/161 NM_001253.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0487
AC:
7414
AN:
152102
Hom.:
348
Cov.:
33
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.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0488
AC:
7433
AN:
152220
Hom.:
354
Cov.:
33
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 submitterclinical testingGeneDxJun 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.

Other links and lift over

dbSNP: rs10948136; hg19: chr6-44360533; COSMIC: COSV65177372; API