Genetic Variant CLSPN:c.3144-36T>C (chr1-35739565-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.37

Publications

16 publications found

Variant links:

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]

CLSPN links:

ENSG00000232335 (HGNC:40896):

ENSG00000232335 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
CLSPN	NM_022111.4 link	c.3144-36T>C	intron_variant	Intron 18 of 24	ENST00000318121.8	NP_071394.2	Q9HAW4-1
CLSPN	NM_001330490.2 link	c.3144-36T>C	intron_variant	Intron 18 of 24		NP_001317419.1	Q9HAW4-3
CLSPN	NM_001190481.2 link	c.2952-36T>C	intron_variant	Intron 17 of 23		NP_001177410.1	Q9HAW4-2
CLSPN-AS1	NR_199043.1 link	n.69+52A>G	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLSPN	ENST00000318121.8 link	c.3144-36T>C		intron_variant	Intron 18 of 24	1	NM_022111.4	ENSP00000312995.3		Q9HAW4-1

Frequencies

GnomAD3 genomes

AF:

0.667

AC:

101322

AN:

151988

Hom.:

38420

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.723

AC:

172010

AN:

237926

AF XY:

0.747

show subpopulations

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 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.:

AF XY:

0.826

AC XY:

579318

AN XY:

701176

show subpopulations

African (AFR)

AF:

0.311

AC:

9862

AN:

31684

American (AMR)

AF:

0.566

AC:

23819

AN:

42050

Ashkenazi Jewish (ASJ)

AF:

0.773

AC:

19152

AN:

24786

East Asian (EAS)

AF:

0.233

AC:

9145

AN:

39204

South Asian (SAS)

AF:

0.796

AC:

65912

AN:

82796

European-Finnish (FIN)

AF:

0.831

AC:

42740

AN:

51424

Middle Eastern (MID)

AF:

0.792

AC:

4445

AN:

5614

European-Non Finnish (NFE)

AF:

0.877

AC:

938465

AN:

1069478

Other (OTH)

AF:

0.775

AC:

45133

AN:

58240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

8544

17087

25631

34174

42718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20010

40020

60030

80040

100050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.666

AC:

101322

AN:

152108

Hom.:

38412

Cov.:

AF XY:

0.662

AC XY:

49196

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.330

AC:

13678

AN:

41474

American (AMR)

AF:

0.619

AC:

9459

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.778

AC:

2699

AN:

3470

East Asian (EAS)

AF:

0.235

AC:

1219

AN:

5184

South Asian (SAS)

AF:

0.778

AC:

3745

AN:

4814

European-Finnish (FIN)

AF:

0.828

AC:

8763

AN:

10578

Middle Eastern (MID)

AF:

0.803

AC:

236

AN:

294

European-Non Finnish (NFE)

AF:

0.872

AC:

59284

AN:

68002

Other (OTH)

AF:

0.693

AC:

1460

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1274

2549

3823

5098

6372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

768

1536

2304

3072

3840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.739

Hom.:

11425

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

(source)

DANN

Benign

0.86

PhyloP100

2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over