Variant rs3741447 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2

The NM_001247997.2(CLIP1):c.2338C>T(p.Arg780Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000332 in 1,614,088 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 8 hom. )

Consequence

CLIP1
NM_001247997.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 4.15

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 -8 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=0.007330656).

BP6

Variant 12-122340866-G-A is Benign according to our data. Variant chr12-122340866-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 434780.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLIP1	NM_001247997.2 linkuse as main transcript	c.2338C>T	p.Arg780Trp	missense_variant	11/26	ENST00000620786.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIP1	ENST00000620786.5 linkuse as main transcript	c.2338C>T	p.Arg780Trp	missense_variant	11/26	5	NM_001247997.2	A1	P30622-3

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00539

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000410

AC:

103

AN:

251340

Hom.:

AF XY:

0.000427

AC XY:

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00337

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000337

AC:

492

AN:

1461846

Hom.:

Cov.:

AF XY:

0.000337

AC XY:

245

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00967

Gnomad4 SAS exome

AF:

0.000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000289

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00540

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000125

Hom.:

Bravo

AF:

0.000159

ExAC

AF:

0.000404

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 01, 2016

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.53

.;.;D;.;.;D

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.036

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.87

.;D;D;D;D;.

M_CAP

Benign

0.020

MetaRNN

Benign

0.0073

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;.;L;.;.;L

MutationTaster

Benign

0.85

D;D;D;D;D

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-3.0

D;D;.;D;.;D

REVEL

Benign

0.053

Sift

Benign

0.053

T;T;.;T;.;T

Sift4G

Uncertain

0.060

T;T;T;T;.;T

Polyphen

0.011

B;B;B;B;.;B

Vest4

0.20

MVP

0.31

MPC

0.28

ClinPred

0.042

GERP RS

2.8

Varity_R

0.061

gMVP

0.23

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