rs6942323

Variant names:

• chr6-44392943-A-G
• rs6942323
• NM_001253.4:c.311+115A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-44392943-A-G
• chr6-44392943-A-T

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.311+115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 842,448 control chromosomes in the GnomAD database, including 266,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.71 (40201 hom., cov: 32)
  • Exomes 𝑓: 0.80 (226452 hom.)
• Consequence: CDC5L NM_001253.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.548
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-44392943-A-G is Benign according to our data. Variant chr6-44392943-A-G is described in ClinVar as Benign. ClinVar VariationId is 1281090.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.856 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.311+115A>G		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.311+115A>G		intron	N/A	ENSP00000360532.3	Q99459
	CDC5L	ENST00000862195.1		c.311+115A>G		intron	N/A	ENSP00000532254.1
	CDC5L	ENST00000918589.1		c.311+115A>G		intron	N/A	ENSP00000588648.1

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107235 AN: 151976 Hom.: 40194 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.727

GnomAD4 exome AF: 0.795 AC: 548988 AN: 690354 Hom.: 226452 AF XY: 0.790 AC XY: 276693 AN XY: 350234

African (AFR) AF: 0.501 AC: 8589 AN: 17138

American (AMR) AF: 0.666 AC: 13743 AN: 20646

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 11907 AN: 14732

East Asian (EAS) AF: 0.282 AC: 9084 AN: 32268

South Asian (SAS) AF: 0.591 AC: 24845 AN: 42022

European-Finnish (FIN) AF: 0.786 AC: 28914 AN: 36800

Middle Eastern (MID) AF: 0.739 AC: 1951 AN: 2640

European-Non Finnish (NFE) AF: 0.865 AC: 424804 AN: 491042

Other (OTH) AF: 0.761 AC: 25151 AN: 33066

GnomAD4 genome AF: 0.705 AC: 107262 AN: 152094 Hom.: 40201 Cov.: 32 AF XY: 0.694 AC XY: 51609 AN XY: 74336

African (AFR) AF: 0.508 AC: 21083 AN: 41472

American (AMR) AF: 0.657 AC: 10030 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2783 AN: 3470

East Asian (EAS) AF: 0.258 AC: 1333 AN: 5176

South Asian (SAS) AF: 0.553 AC: 2662 AN: 4818

European-Finnish (FIN) AF: 0.774 AC: 8177 AN: 10570

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

European-Non Finnish (NFE) AF: 0.862 AC: 58634 AN: 68000

Other (OTH) AF: 0.724 AC: 1527 AN: 2110

Alfa AF: 0.781 Hom.: 5913

Bravo AF: 0.688

Asia WGS AF: 0.386 AC: 1348 AN: 3476

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	-0.90
CADD	Benign	0.54
DANN	Benign	0.55
PhyloP100		-0.55
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: rs6942323; hg19: chr6-44360680;