NM_001253.4:c.2091+7606G>T

Variant names:

• chr6-44437516-G-T
• rs10484624
• NM_001253.4:c.2091+7606G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001253.4(CDC5L):​c.2091+7606G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0364 in 152,132 control chromosomes in the GnomAD database, including 211 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 0.036 (211 hom., cov: 32)
• Consequence: CDC5L NM_001253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0921 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC5L	NM_001253.4	MANE Select	c.2091+7606G>T		intron	N/A	NP_001244.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC5L	ENST00000371477.4	TSL:1 MANE Select	c.2091+7606G>T		intron	N/A	ENSP00000360532.3

Frequencies

GnomAD3 genomes AF: 0.0362 AC: 5497 AN: 152014 Hom.: 203 Cov.: 32

Gnomad AFR AF: 0.0939

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0221

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.0384

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.00142

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.0392

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

GnomAD4 genome AF: 0.0364 AC: 5534 AN: 152132 Hom.: 211 Cov.: 32 AF XY: 0.0362 AC XY: 2692 AN XY: 74368

African (AFR) AF: 0.0945 AC: 3919 AN: 41454

American (AMR) AF: 0.0220 AC: 337 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0418 AC: 145 AN: 3468

East Asian (EAS) AF: 0.0387 AC: 201 AN: 5190

South Asian (SAS) AF: 0.0255 AC: 123 AN: 4818

European-Finnish (FIN) AF: 0.00142 AC: 15 AN: 10588

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0102 AC: 691 AN: 68010

Other (OTH) AF: 0.0388 AC: 82 AN: 2112

Alfa AF: 0.0179 Hom.: 73

Bravo AF: 0.0404

Asia WGS AF: 0.0390 AC: 134 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.56
PhyloP100		-0.095
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10484624; hg19: chr6-44405253;