6-44387962-T-C

Variant names:

• chr6-44387962-T-C
• rs2297331
• NM_001253.4:c.45+94T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

ENSG00000296265 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.45+94T>C		intron	N/A	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.45+94T>C		intron	N/A	ENSP00000360532.3	Q99459
	CDC5L	ENST00000862195.1		c.45+94T>C		intron	N/A	ENSP00000532254.1
	CDC5L	ENST00000918589.1		c.45+94T>C		intron	N/A	ENSP00000588648.1

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

African (AFR) AF: 0.558 AC: 13607 AN: 24406

American (AMR) AF: 0.664 AC: 21144 AN: 31840

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 18838 AN: 22552

East Asian (EAS) AF: 0.281 AC: 9582 AN: 34052

South Asian (SAS) AF: 0.597 AC: 42947 AN: 71976

European-Finnish (FIN) AF: 0.791 AC: 35719 AN: 45182

Middle Eastern (MID) AF: 0.741 AC: 3235 AN: 4364

European-Non Finnish (NFE) AF: 0.864 AC: 680060 AN: 786682

Other (OTH) AF: 0.767 AC: 35973 AN: 46922

GnomAD4 genome AF: 0.722 AC: 109887 AN: 152166 Hom.: 41640 Cov.: 32 AF XY: 0.710 AC XY: 52820 AN XY: 74390

African (AFR) AF: 0.563 AC: 23382 AN: 41512

American (AMR) AF: 0.663 AC: 10145 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2885 AN: 3472

East Asian (EAS) AF: 0.259 AC: 1331 AN: 5140

South Asian (SAS) AF: 0.555 AC: 2674 AN: 4820

European-Finnish (FIN) AF: 0.775 AC: 8208 AN: 10594

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.863 AC: 58672 AN: 68004

Other (OTH) AF: 0.737 AC: 1557 AN: 2114

Alfa AF: 0.782 Hom.: 6144

Bravo AF: 0.708

Asia WGS AF: 0.387 AC: 1350 AN: 3478

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	-0.79
CADD	Benign	0.13
DANN	Benign	0.64
PhyloP100		-1.6
PromoterAI		-0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
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: rs2297331; hg19: chr6-44355699; COSMIC: COSV65176302;