1-35739565-A-G

Position:

• chr1-35739565-A-G

Variant summary

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

The NM_022111.4(CLSPN):​c.3144-36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 1,557,384 control chromosomes in the GnomAD database, including 531,203 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 (38412 hom., cov: 32)
  • Exomes 𝑓: 0.82 (492791 hom.)
• Consequence: CLSPN NM_022111.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.37

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]

ENSG00000232335 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• 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	Protein	UniProt
CLSPN	NM_022111.4	c.3144-36T>C		intron_variant		ENST00000318121.8	NP_071394.2
CLSPN	NM_001330490.2	c.3144-36T>C		intron_variant			NP_001317419.1
CLSPN	NM_001190481.2	c.2952-36T>C		intron_variant			NP_001177410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLSPN	ENST00000318121.8	c.3144-36T>C		intron_variant		1	NM_022111.4	ENSP00000312995.3

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101322 AN: 151988 Hom.: 38420 Cov.: 32

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: 0.828

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.692

GnomAD3 exomes AF: 0.723 AC: 172010 AN: 237926 Hom.: 68059 AF XY: 0.747 AC XY: 96110 AN XY: 128702

Gnomad AFR exome AF: 0.318

Gnomad AMR exome AF: 0.556

Gnomad ASJ exome AF: 0.782

Gnomad EAS exome AF: 0.204

Gnomad SAS exome AF: 0.797

Gnomad FIN exome AF: 0.828

Gnomad NFE exome AF: 0.871

Gnomad OTH exome AF: 0.780

GnomAD4 exome AF: 0.825 AC: 1158673 AN: 1405276 Hom.: 492791 Cov.: 21 AF XY: 0.826 AC XY: 579318 AN XY: 701176

Gnomad4 AFR exome AF: 0.311

Gnomad4 AMR exome AF: 0.566

Gnomad4 ASJ exome AF: 0.773

Gnomad4 EAS exome AF: 0.233

Gnomad4 SAS exome AF: 0.796

Gnomad4 FIN exome AF: 0.831

Gnomad4 NFE exome AF: 0.877

Gnomad4 OTH exome AF: 0.775

GnomAD4 genome AF: 0.666 AC: 101322 AN: 152108 Hom.: 38412 Cov.: 32 AF XY: 0.662 AC XY: 49196 AN XY: 74360

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.778

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.828

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.693

Alfa AF: 0.747 Hom.: 11372

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	-0.71
CADD	Benign	11
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs577483; hg19: chr1-36205166; COSMIC: COSV52056808; COSMIC: COSV52056808;