rs535638

Positions:

• chr1-35751234-C-T

Variant summary

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

The NM_022111.4(CLSPN):​c.2028+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 1,593,610 control chromosomes in the GnomAD database, including 542,847 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 0.67 (38375 hom., cov: 28)
  • Exomes 𝑓: 0.82 (504472 hom.)
• Consequence: CLSPN NM_022111.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411

Genes affected

CLSPN (HGNC:19715): (claspin) The product of this gene is an essential upstream regulator of checkpoint kinase 1 and triggers a checkpoint arrest of the cell cycle in response to replicative stress or DNA damage. The protein is also required for efficient DNA replication during a normal S phase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLSPN	NM_022111.4	c.2028+16G>A		intron_variant		ENST00000318121.8
CLSPN	NM_001190481.2	c.1836+16G>A		intron_variant
CLSPN	NM_001330490.2	c.2028+16G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLSPN	ENST00000318121.8	c.2028+16G>A		intron_variant		1	NM_022111.4	P2
CLSPN	ENST00000251195.9	c.2028+16G>A		intron_variant		1		A2
CLSPN	ENST00000373220.7	c.1836+16G>A		intron_variant		1		A2
CLSPN	ENST00000520551.1	c.2028+16G>A		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101185 AN: 151622 Hom.: 38383 Cov.: 28

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.818

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.692

GnomAD3 exomes AF: 0.719 AC: 169752 AN: 235992 Hom.: 66973 AF XY: 0.745 AC XY: 95614 AN XY: 128368

Gnomad AFR exome AF: 0.317

Gnomad AMR exome AF: 0.550

Gnomad ASJ exome AF: 0.781

Gnomad EAS exome AF: 0.201

Gnomad SAS exome AF: 0.794

Gnomad FIN exome AF: 0.837

Gnomad NFE exome AF: 0.871

Gnomad OTH exome AF: 0.781

GnomAD4 exome AF: 0.823 AC: 1187027 AN: 1441870 Hom.: 504472 Cov.: 38 AF XY: 0.825 AC XY: 592174 AN XY: 717724

Gnomad4 AFR exome AF: 0.305

Gnomad4 AMR exome AF: 0.562

Gnomad4 ASJ exome AF: 0.772

Gnomad4 EAS exome AF: 0.232

Gnomad4 SAS exome AF: 0.794

Gnomad4 FIN exome AF: 0.836

Gnomad4 NFE exome AF: 0.876

Gnomad4 OTH exome AF: 0.773

GnomAD4 genome AF: 0.667 AC: 101185 AN: 151740 Hom.: 38375 Cov.: 28 AF XY: 0.662 AC XY: 49094 AN XY: 74114

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.778

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.830

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.693

Alfa AF: 0.805 Hom.: 28279

Bravo AF: 0.627

Asia WGS AF: 0.533 AC: 1859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.28
DANN	Benign	0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97

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: rs535638; hg19: chr1-36216835; COSMIC: COSV52049327; COSMIC: COSV52049327;