6-44417704-A-G

Position:

• chr6-44417704-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001253.4(CDC5L):​c.1093-1745A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,244 control chromosomes in the GnomAD database, including 1,023 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (1023 hom., cov: 32)
• Consequence: CDC5L NM_001253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC5L	NM_001253.4	c.1093-1745A>G		intron_variant		ENST00000371477.4	NP_001244.1
POLR1C	NM_001318876.2	c.946-24186A>G		intron_variant			NP_001305805.1
CDC5L	XM_047419605.1	c.658-1745A>G		intron_variant			XP_047275561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC5L	ENST00000371477.4	c.1093-1745A>G		intron_variant		1	NM_001253.4	ENSP00000360532	P1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15544 AN: 152126 Hom.: 1023 Cov.: 32

Gnomad AFR AF: 0.0441

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0869

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0702

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.102 AC: 15537 AN: 152244 Hom.: 1023 Cov.: 32 AF XY: 0.0983 AC XY: 7320 AN XY: 74436

Gnomad4 AFR AF: 0.0440

Gnomad4 AMR AF: 0.0867

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0708

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.128

Alfa AF: 0.136 Hom.: 2206

Bravo AF: 0.0994

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.78
DANN	Benign	0.65

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: rs13198841; hg19: chr6-44385441;