6-44387962-T-C

Position:

• chr6-44387962-T-C

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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.55

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:20194): (RNA polymerase I and III subunit C) The protein encoded by this gene is a subunit of both RNA polymerase I and RNA polymerase III complexes. The encoded protein is part of the Pol core element. Mutations in this gene have been associated with Treacher Collins syndrome (TCS) and hypomyelinating leukodystrophy 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

LOC124901323 (HGNC:):

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC5L	NM_001253.4	c.45+94T>C		intron_variant		ENST00000371477.4	NP_001244.1
POLR1C	NM_001318876.2	c.946-53928T>C		intron_variant			NP_001305805.1
LOC124901323	XR_007059595.1	n.-43A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC5L	ENST00000371477.4	c.45+94T>C		intron_variant		1	NM_001253.4	ENSP00000360532.3

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109856 AN: 152048 Hom.: 41635 Cov.: 32

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

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.: 32 AF XY: 0.710 AC XY: 52820 AN XY: 74390

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

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

Other links and lift over

dbSNP: rs2297331; hg19: chr6-44355699; COSMIC: COSV65176302;