Variant rs138030919 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The NM_001247997.2(CLIP1):c.425C>T(p.Ala142Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,613,854 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

CLIP1
NM_001247997.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.49

Variant links:

Genes affected

CLIP1 (HGNC:10461): (CAP-Gly domain containing linker protein 1) The protein encoded by this gene links endocytic vesicles to microtubules. This gene is highly expressed in Reed-Sternberg cells of Hodgkin disease. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

CLIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CLIP1. . Trascript score misZ 3.4483 (greater than threshold 3.09). GenCC has associacion of gene with autosomal recessive non-syndromic intellectual disability, intellectual disability.

BP4

Computational evidence support a benign effect (MetaRNN=0.02245453).

BS2

High AC in GnomAd4 at 88 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIP1	NM_001247997.2 linkuse as main transcript	c.425C>T	p.Ala142Val	missense_variant	3/26	ENST00000620786.5	NP_001234926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLIP1	ENST00000620786.5 linkuse as main transcript	c.425C>T	p.Ala142Val	missense_variant	3/26	5	NM_001247997.2	ENSP00000479322	A1	P30622-3

Frequencies

GnomAD3 genomes

AF:

0.000580

AC:

AN:

151854

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000582

AC:

146

AN:

251064

Hom.:

AF XY:

0.000538

AC XY:

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.00142

AC:

2071

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

970

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00176

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.000579

AC:

AN:

151972

Hom.:

Cov.:

AF XY:

0.000485

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000284

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00112

Hom.:

Bravo

AF:

0.000563

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.000552

AC:

EpiCase

AF:

0.00125

EpiControl

AF:

0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 30, 2016

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

.;.;.;T;.;T;T

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

D;.;D;D;D;.;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.022

T;T;T;T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.7

.;L;L;L;L;L;.

MutationTaster

Benign

0.78

N;N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.83

N;N;N;.;N;N;N

REVEL

Benign

0.16

Sift

Benign

0.25

T;T;T;.;T;T;T

Sift4G

Benign

0.22

T;T;T;T;T;T;.

Polyphen

0.0

.;B;B;B;B;B;.

Vest4

0.072

MVP

0.42

MPC

1.2

ClinPred

0.027

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.031

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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