2-121530869-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001395891.1(CLASP1):c.196-544G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0451 in 678,710 control chromosomes in the GnomAD database, including 903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 157 hom., cov: 32)

Exomes 𝑓: 0.047 ( 746 hom. )

Consequence

CLASP1
NM_001395891.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -7.95

Publications

1 publications found

Variant links:

Genes affected

CLASP1 (HGNC:17088): (cytoplasmic linker associated protein 1) CLASPs, such as CLASP1, are nonmotor microtubule-associated proteins that interact with CLIPs (e.g., CLIP170; MIM 179838). CLASP1 is involved in the regulation of microtubule dynamics at the kinetochore and throughout the spindle (Maiato et al., 2003 [PubMed 12837247]).[supplied by OMIM, Mar 2008]

CLASP1 links:

CLASP1-AS1 (HGNC:55328): (CLASP1 antisense RNA 1)

CLASP1-AS1 links:

RNU4ATAC (HGNC:34016): (RNA, U4atac small nuclear) The small nuclear RNA (snRNA) encoded by this gene is part of the U12-dependent minor spliceosome complex. In addition to the encoded RNA, this ribonucleoprotein complex consists of U11, U12, U5, and U6atac snRNAs. The U12-dependent spliceosome acts on approximately 700 specific introns in the human genome. Defects in this gene are a cause of microcephalic osteodysplastic primordial dwarfism type 1 (MOPD). [provided by RefSeq, Jul 2011]

RNU4ATAC Gene-Disease associations (from GenCC):

microcephalic osteodysplastic primordial dwarfism type I
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
RNU4ATAC spectrum disorder
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, PanelApp Australia, Broad Center for Mendelian Genomics, Ambry Genetics
Roifman syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
Lowry-Wood syndrome
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

RNU4ATAC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 2-121530869-C-T is Benign according to our data. Variant chr2-121530869-C-T is described in ClinVar as Benign. ClinVar VariationId is 1274763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395891.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLASP1	NM_001395891.1	MANE Select	c.196-544G>A	intron	N/A	NP_001382820.1	A0A8V8TLP7
CLASP1	NM_015282.3		c.196-544G>A	intron	N/A	NP_056097.1	Q7Z460-1
CLASP1	NM_001378003.1		c.196-544G>A	intron	N/A	NP_001364932.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLASP1	ENST00000696935.1	MANE Select	c.196-544G>A	intron	N/A	ENSP00000512981.1	A0A8V8TLP7
CLASP1	ENST00000263710.8	TSL:5	c.196-544G>A	intron	N/A	ENSP00000263710.4	Q7Z460-1
CLASP1	ENST00000961911.1		c.196-544G>A	intron	N/A	ENSP00000631970.1

Frequencies

GnomAD3 genomes

AF:

0.0385

AC:

5861

AN:

152190

Hom.:

156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0196

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0381

Gnomad ASJ

AF:

0.0637

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.0536

Gnomad FIN

AF:

0.0248

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0423

Gnomad OTH

AF:

0.0311

GnomAD2 exomes

AF:

0.0512

AC:

6485

AN:

126736

AF XY:

0.0505

show subpopulations

Gnomad AFR exome

AF:

0.0156

Gnomad AMR exome

AF:

0.0526

Gnomad ASJ exome

AF:

0.0596

Gnomad EAS exome

AF:

0.131

Gnomad FIN exome

AF:

0.0268

Gnomad NFE exome

AF:

0.0420

Gnomad OTH exome

AF:

0.0487

GnomAD4 exome

AF:

0.0470

AC:

24755

AN:

526402

Hom.:

746

Cov.:

AF XY:

0.0469

AC XY:

13216

AN XY:

281904

show subpopulations

African (AFR)

AF:

0.0189

AC:

286

AN:

15168

American (AMR)

AF:

0.0508

AC:

1698

AN:

33412

Ashkenazi Jewish (ASJ)

AF:

0.0566

AC:

1112

AN:

19638

East Asian (EAS)

AF:

0.115

AC:

3645

AN:

31580

South Asian (SAS)

AF:

0.0470

AC:

2896

AN:

61590

European-Finnish (FIN)

AF:

0.0285

AC:

940

AN:

32952

Middle Eastern (MID)

AF:

0.0241

AC:

AN:

2364

European-Non Finnish (NFE)

AF:

0.0425

AC:

12764

AN:

300370

Other (OTH)

AF:

0.0463

AC:

1357

AN:

29328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1197

2395

3592

4790

5987

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

220

330

440

550

<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:

0.0385

AC:

5865

AN:

152308

Hom.:

157

Cov.:

AF XY:

0.0377

AC XY:

2808

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0197

AC:

818

AN:

41572

American (AMR)

AF:

0.0383

AC:

586

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0637

AC:

221

AN:

3472

East Asian (EAS)

AF:

0.139

AC:

718

AN:

5172

South Asian (SAS)

AF:

0.0533

AC:

257

AN:

4826

European-Finnish (FIN)

AF:

0.0248

AC:

263

AN:

10614

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0423

AC:

2880

AN:

68030

Other (OTH)

AF:

0.0308

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

289

578

866

1155

1444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0240

Hom.:

Bravo

AF:

0.0401

Asia WGS

AF:

0.0670

AC:

235

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

CLASP1-related disorder (1)

RNU4ATAC-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.0010

(source)

DANN

Benign

0.75

PhyloP100

-7.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over