6-44390707-T-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.149+336T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,182 control chromosomes in the GnomAD database, including 1,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1590 hom., cov: 32)
• Consequence: CDC5L NM_001253.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.365

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=-0.78).
• BP6: Variant 6-44390707-T-G is Benign according to our data. Variant chr6-44390707-T-G is described in ClinVar as [Benign]. Clinvar id is 1275507.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC5L	NM_001253.4	c.149+336T>G		intron_variant		ENST00000371477.4
POLR1C	NM_001318876.2	c.946-51183T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC5L	ENST00000371477.4	c.149+336T>G		intron_variant		1	NM_001253.4	P1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16153 AN: 152068 Hom.: 1588 Cov.: 32

Gnomad AFR AF: 0.0669

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0783

Gnomad OTH AF: 0.101

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.106 AC: 16143 AN: 152182 Hom.: 1590 Cov.: 32 AF XY: 0.113 AC XY: 8422 AN XY: 74418

Gnomad4 AFR AF: 0.0667

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.0783

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0883 Hom.: 119

Bravo AF: 0.102

Asia WGS AF: 0.412 AC: 1431 AN: 3478

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	8.1
Dann	Benign	0.75

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: rs9369481; hg19: chr6-44358444;