6-44390707-T-G

Position:

• chr6-44390707-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: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=-0.78).
• 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	Protein	UniProt
CDC5L	NM_001253.4	c.149+336T>G		intron_variant		ENST00000371477.4	NP_001244.1
POLR1C	NM_001318876.2	c.946-51183T>G		intron_variant			NP_001305805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC5L	ENST00000371477.4	c.149+336T>G		intron_variant		1	NM_001253.4	ENSP00000360532.3

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

- -

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;