rs535638

Variant names:

• chr1-35751234-C-T
• rs535638
• NM_022111.4:c.2028+16G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022111.4. 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
	CLSPN	NM_022111.4	MANE Select	c.2028+16G>A		intron	N/A	NP_071394.2
	CLSPN	NM_001330490.2		c.2028+16G>A		intron	N/A	NP_001317419.1
	CLSPN	NM_001190481.2		c.1836+16G>A		intron	N/A	NP_001177410.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLSPN	ENST00000318121.8	TSL:1 MANE Select	c.2028+16G>A		intron	N/A	ENSP00000312995.3
	CLSPN	ENST00000251195.9	TSL:1	c.2028+16G>A		intron	N/A	ENSP00000251195.5
	CLSPN	ENST00000520551.1	TSL:1	c.2028+16G>A		intron	N/A	ENSP00000428848.1

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

GnomAD2 exomes AF: 0.719 AC: 169752 AN: 235992 AF XY: 0.745

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 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

African (AFR) AF: 0.305 AC: 10093 AN: 33078

American (AMR) AF: 0.562 AC: 24708 AN: 44002

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 20012 AN: 25928

East Asian (EAS) AF: 0.232 AC: 9193 AN: 39656

South Asian (SAS) AF: 0.794 AC: 67800 AN: 85354

European-Finnish (FIN) AF: 0.836 AC: 32781 AN: 39214

Middle Eastern (MID) AF: 0.788 AC: 4059 AN: 5152

European-Non Finnish (NFE) AF: 0.876 AC: 972009 AN: 1109488

Other (OTH) AF: 0.773 AC: 46372 AN: 59998

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

African (AFR) AF: 0.330 AC: 13646 AN: 41340

American (AMR) AF: 0.620 AC: 9450 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2698 AN: 3468

East Asian (EAS) AF: 0.235 AC: 1197 AN: 5100

South Asian (SAS) AF: 0.778 AC: 3724 AN: 4786

European-Finnish (FIN) AF: 0.830 AC: 8758 AN: 10556

Middle Eastern (MID) AF: 0.808 AC: 236 AN: 292

European-Non Finnish (NFE) AF: 0.872 AC: 59237 AN: 67940

Other (OTH) AF: 0.693 AC: 1460 AN: 2106

Alfa AF: 0.804 Hom.: 31127

Bravo AF: 0.627

Asia WGS AF: 0.533 AC: 1859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.28
DANN	Benign	0.30
PhyloP100		-0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97
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: rs535638; hg19: chr1-36216835; COSMIC: COSV52049327; COSMIC: COSV52049327;