Variant 2-121367797-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BA1

The NM_001395891.1(CLASP1):c.3740C>A(p.Thr1247Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00371 in 1,613,780 control chromosomes in the GnomAD database, including 267 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0072 ( 44 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 223 hom. )

Consequence

CLASP1
NM_001395891.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.28

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CLASP1. . Gene score misZ 3.6133 (greater than the threshold 3.09). GenCC has associacion of gene with complex neurodevelopmental disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016407967).

BP6

Variant 2-121367797-G-T is Benign according to our data. Variant chr2-121367797-G-T is described in ClinVar as [Benign]. Clinvar id is 3037345.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLASP1	NM_001395891.1 linkuse as main transcript	c.3740C>A	p.Thr1247Asn	missense_variant	36/41	ENST00000696935.1	NP_001382820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLASP1	ENST00000696935.1 linkuse as main transcript	c.3740C>A	p.Thr1247Asn	missense_variant	36/41		NM_001395891.1	ENSP00000512981	A2

Frequencies

GnomAD3 genomes

AF:

0.00724

AC:

1102

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0625

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0104

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.0142

AC:

3521

AN:

248660

Hom.:

165

AF XY:

0.0106

AC XY:

1430

AN XY:

134982

show subpopulations

Gnomad AFR exome

AF:

0.000971

Gnomad AMR exome

AF:

0.0916

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.0149

Gnomad SAS exome

AF:

0.000556

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.00878

GnomAD4 exome

AF:

0.00334

AC:

4880

AN:

1461454

Hom.:

223

Cov.:

AF XY:

0.00285

AC XY:

2074

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.0908

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.0117

Gnomad4 SAS exome

AF:

0.000417

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000396

Gnomad4 OTH exome

AF:

0.00381

GnomAD4 genome

AF:

0.00725

AC:

1104

AN:

152326

Hom.:

Cov.:

AF XY:

0.00798

AC XY:

594

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00161

Gnomad4 AMR

AF:

0.0625

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0104

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00143

Hom.:

Bravo

AF:

0.0122

ESP6500AA

AF:

0.000767

AC:

ESP6500EA

AF:

0.000241

AC:

ExAC

AF:

0.0104

AC:

1252

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CLASP1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 11, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.51

DEOGEN2

Benign

0.030

T;.;.;T;.;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.069

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

.;D;D;D;D;D

MetaRNN

Benign

0.0016

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;.;.;L;.;.

MutationTaster

Benign

0.65

D;D;D;D;D;D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.74

.;N;.;N;N;.

REVEL

Benign

0.054

Sift

Benign

0.41

.;T;.;T;T;.

Sift4G

Benign

0.25

.;T;T;T;T;T

Polyphen

0.15

B;.;.;B;.;.

Vest4

0.31, 0.40, 0.30, 0.41

MPC

0.46

ClinPred

0.022

GERP RS

5.1

Varity_R

0.12

gMVP

0.27

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over