chr6-44392943-A-G

Position:

• chr6-44392943-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001253.4(CDC5L):​c.311+115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 842,448 control chromosomes in the GnomAD database, including 266,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.71 (40201 hom., cov: 32)
  • Exomes 𝑓: 0.80 (226452 hom.)
• Consequence: CDC5L NM_001253.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.548

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]

POLR1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-44392943-A-G is Benign according to our data. Variant chr6-44392943-A-G is described in ClinVar as [Benign]. Clinvar id is 1281090.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC5L	NM_001253.4	c.311+115A>G		intron_variant		ENST00000371477.4	NP_001244.1
POLR1C	NM_001318876.2	c.946-48947A>G		intron_variant			NP_001305805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC5L	ENST00000371477.4	c.311+115A>G		intron_variant		1	NM_001253.4	ENSP00000360532	P1

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107235 AN: 151976 Hom.: 40194 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.727

GnomAD4 exome AF: 0.795 AC: 548988 AN: 690354 Hom.: 226452 AF XY: 0.790 AC XY: 276693 AN XY: 350234

Gnomad4 AFR exome AF: 0.501

Gnomad4 AMR exome AF: 0.666

Gnomad4 ASJ exome AF: 0.808

Gnomad4 EAS exome AF: 0.282

Gnomad4 SAS exome AF: 0.591

Gnomad4 FIN exome AF: 0.786

Gnomad4 NFE exome AF: 0.865

Gnomad4 OTH exome AF: 0.761

GnomAD4 genome AF: 0.705 AC: 107262 AN: 152094 Hom.: 40201 Cov.: 32 AF XY: 0.694 AC XY: 51609 AN XY: 74336

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.802

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.774

Gnomad4 NFE AF: 0.862

Gnomad4 OTH AF: 0.724

Alfa AF: 0.781 Hom.: 5913

Bravo AF: 0.688

Asia WGS AF: 0.386 AC: 1348 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	-0.90
CADD	Benign	0.54
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs6942323; hg19: chr6-44360680;