chr6-44403977-C-T

Variant names:

• chr6-44403977-C-T
• rs6934058
• NM_001253.4:c.708C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001253.4(CDC5L):​c.708C>T​(p.Asp236Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,612,186 control chromosomes in the GnomAD database, including 20,485 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2743 hom., cov: 32)
  • Exomes 𝑓: 0.12 (17742 hom.)
• Consequence: CDC5L NM_001253.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.25
• Publications: 23 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 6-44403977-C-T is Benign according to our data. Variant chr6-44403977-C-T is described in ClinVar as Benign. ClinVar VariationId is 1228167.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.25 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001253.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC5L	NM_001253.4	MANE Select	c.708C>T	p.Asp236Asp	synonymous	Exon 6 of 16	NP_001244.1	Q99459

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC5L	ENST00000371477.4	TSL:1 MANE Select	c.708C>T	p.Asp236Asp	synonymous	Exon 6 of 16	ENSP00000360532.3	Q99459
	CDC5L	ENST00000862195.1		c.708C>T	p.Asp236Asp	synonymous	Exon 6 of 15	ENSP00000532254.1
	CDC5L	ENST00000918589.1		c.708C>T	p.Asp236Asp	synonymous	Exon 6 of 16	ENSP00000588648.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23119 AN: 151712 Hom.: 2741 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0836

Gnomad OTH AF: 0.130

GnomAD2 exomes AF: 0.170 AC: 42594 AN: 250284 AF XY: 0.173

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.121

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.623

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.0821

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.119 AC: 173310 AN: 1460356 Hom.: 17742 Cov.: 32 AF XY: 0.123 AC XY: 89591 AN XY: 726382

African (AFR) AF: 0.212 AC: 7082 AN: 33378

American (AMR) AF: 0.123 AC: 5496 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2840 AN: 26114

East Asian (EAS) AF: 0.576 AC: 22849 AN: 39654

South Asian (SAS) AF: 0.307 AC: 26334 AN: 85754

European-Finnish (FIN) AF: 0.122 AC: 6490 AN: 53392

Middle Eastern (MID) AF: 0.102 AC: 591 AN: 5766

European-Non Finnish (NFE) AF: 0.0835 AC: 92751 AN: 1111392

Other (OTH) AF: 0.147 AC: 8877 AN: 60346

GnomAD4 genome AF: 0.152 AC: 23141 AN: 151830 Hom.: 2743 Cov.: 32 AF XY: 0.160 AC XY: 11852 AN XY: 74178

African (AFR) AF: 0.211 AC: 8719 AN: 41346

American (AMR) AF: 0.123 AC: 1881 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 395 AN: 3472

East Asian (EAS) AF: 0.611 AC: 3159 AN: 5170

South Asian (SAS) AF: 0.348 AC: 1674 AN: 4816

European-Finnish (FIN) AF: 0.119 AC: 1253 AN: 10494

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0836 AC: 5684 AN: 67976

Other (OTH) AF: 0.134 AC: 283 AN: 2110

Alfa AF: 0.108 Hom.: 2321

Bravo AF: 0.153

Asia WGS AF: 0.476 AC: 1652 AN: 3478

EpiCase AF: 0.0817

EpiControl AF: 0.0790

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.9
DANN	Benign	0.59
PhyloP100		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6934058; hg19: chr6-44371714; COSMIC: COSV65176122;