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: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]

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	ENSP00000360532.3

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;