Variant rs140092191 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.7A>G(p.Met3Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,610,882 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00097 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 5 hom. )

Consequence

CLIP1
NM_001247997.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21

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=0.011199325).

BS2

High AC in GnomAd4 at 148 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIP1	NM_001247997.2 linkuse as main transcript	c.7A>G	p.Met3Val	missense_variant	2/26	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.7A>G	p.Met3Val	missense_variant	2/26	5	NM_001247997.2	ENSP00000479322	A1	P30622-3

Frequencies

GnomAD3 genomes

AF:

0.000972

AC:

148

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00123

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.000808

AC:

201

AN:

248842

Hom.:

AF XY:

0.000854

AC XY:

115

AN XY:

134594

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.00230

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000964

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00111

AC:

1626

AN:

1458560

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

805

AN XY:

725806

show subpopulations

Gnomad4 AFR exome

AF:

0.0000901

Gnomad4 AMR exome

AF:

0.00221

Gnomad4 ASJ exome

AF:

0.000192

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000563

Gnomad4 NFE exome

AF:

0.00130

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.000972

AC:

148

AN:

152322

Hom.:

Cov.:

AF XY:

0.000953

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00123

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.000960

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000576

AC:

EpiCase

AF:

0.00121

EpiControl

AF:

0.00125

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 31, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.14

CADD

Benign

8.0

DANN

Benign

0.94

DEOGEN2

Benign

0.29

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

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.83

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

M_CAP

Benign

0.019

MetaRNN

Benign

0.011

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

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.1

.;M;M;M;M;M;.;.;.

MutationTaster

Benign

0.97

N;N;N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.2

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

REVEL

Benign

0.15

Sift

Uncertain

0.025

D;T;T;.;T;T;D;D;T

Sift4G

Benign

0.40

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

Polyphen

0.023, 0.0080, 0.013

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

Vest4

0.22

MVP

0.78

MPC

0.42

ClinPred

0.022

GERP RS

1.3

Varity_R

0.16

gMVP

0.41

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