dbSNP rs111741835: CLASP1:c.196-554A>G (chr2-121530879-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001395891.1(CLASP1):c.196-554A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000845 in 692,064 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00043 ( 1 hom. )

Consequence

CLASP1
NM_001395891.1 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.287

Publications

0 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 2-121530879-T-C is Benign according to our data. Variant chr2-121530879-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3033988.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00232 (354/152290) while in subpopulation AFR AF = 0.00782 (325/41556). AF 95% confidence interval is 0.00712. There are 2 homozygotes in GnomAd4. There are 176 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 354 AD gene.

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.196-554A>G	intron	N/A	NP_001382820.1	A0A8V8TLP7
CLASP1	NM_015282.3		c.196-554A>G	intron	N/A	NP_056097.1	Q7Z460-1
CLASP1	NM_001378003.1		c.196-554A>G	intron	N/A	NP_001364932.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLASP1	ENST00000696935.1	MANE Select	c.196-554A>G	intron	N/A	ENSP00000512981.1	A0A8V8TLP7
CLASP1	ENST00000263710.8	TSL:5	c.196-554A>G	intron	N/A	ENSP00000263710.4	Q7Z460-1
CLASP1	ENST00000961911.1		c.196-554A>G	intron	N/A	ENSP00000631970.1

Frequencies

GnomAD3 genomes

AF:

0.00233

AC:

354

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00784

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000580

AC:

AN:

129362

AF XY:

0.000439

show subpopulations

Gnomad AFR exome

AF:

0.00658

Gnomad AMR exome

AF:

0.000708

Gnomad ASJ exome

AF:

0.000125

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000243

Gnomad OTH exome

AF:

0.00101

GnomAD4 exome

AF:

0.000428

AC:

231

AN:

539774

Hom.:

Cov.:

AF XY:

0.000354

AC XY:

103

AN XY:

290978

show subpopulations

African (AFR)

AF:

0.00735

AC:

114

AN:

15520

American (AMR)

AF:

0.000700

AC:

AN:

34300

Ashkenazi Jewish (ASJ)

AF:

0.0000503

AC:

AN:

19886

East Asian (EAS)

AF:

0.0000942

AC:

AN:

31856

South Asian (SAS)

AF:

0.000289

AC:

AN:

62388

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33120

Middle Eastern (MID)

AF:

0.00124

AC:

AN:

2416

European-Non Finnish (NFE)

AF:

0.000148

AC:

AN:

310292

Other (OTH)

AF:

0.000733

AC:

AN:

29996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00232

AC:

354

AN:

152290

Hom.:

Cov.:

AF XY:

0.00236

AC XY:

176

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00782

AC:

325

AN:

41556

American (AMR)

AF:

0.000849

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68010

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000359

Hom.:

Bravo

AF:

0.00246

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

CLASP1-related disorder (1)

RNU4ATAC-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.57

(source)

DANN

Benign

0.74

PhyloP100

-0.29

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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