dbSNP rs1633399: CLTCL1:p.Ile1394Thr (chr22-19196276-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_007098.4(CLTCL1):c.4181T>C(p.Ile1394Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0655 in 1,613,068 control chromosomes in the GnomAD database, including 3,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.059 ( 330 hom., cov: 33)

Exomes 𝑓: 0.066 ( 3364 hom. )

Consequence

CLTCL1
NM_007098.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.61

Variant links:

Genes affected

CLTCL1 (HGNC:2093): (clathrin heavy chain like 1) This gene is a member of the clathrin heavy chain family and encodes a major protein of the polyhedral coat of coated pits and vesicles. Chromosomal aberrations involving this gene are associated with meningioma, DiGeorge syndrome, and velo-cardio-facial syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

CLTCL1 links:

ENSG00000286367 (HGNC:):

ENSG00000286367 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033106506).

BP6

Variant 22-19196276-A-G is Benign according to our data. Variant chr22-19196276-A-G is described in ClinVar as [Benign]. Clinvar id is 3059365.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLTCL1	NM_007098.4 link	c.4181T>C	p.Ile1394Thr	missense_variant	Exon 26 of 33	ENST00000427926.6	NP_009029.3	P53675-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLTCL1	ENST00000427926.6 link	c.4181T>C	p.Ile1394Thr	missense_variant	Exon 26 of 33	1	NM_007098.4	ENSP00000441158.1		P53675-1

Frequencies

GnomAD3 genomes

AF:

0.0589

AC:

8957

AN:

152088

Hom.:

330

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0396

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0827

Gnomad ASJ

AF:

0.0648

Gnomad EAS

AF:

0.0491

Gnomad SAS

AF:

0.0412

Gnomad FIN

AF:

0.0452

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.0688

Gnomad OTH

AF:

0.0747

GnomAD3 exomes

AF:

0.0654

AC:

16226

AN:

248290

Hom.:

559

AF XY:

0.0635

AC XY:

8558

AN XY:

134758

show subpopulations

Gnomad AFR exome

AF:

0.0412

Gnomad AMR exome

AF:

0.0994

Gnomad ASJ exome

AF:

0.0628

Gnomad EAS exome

AF:

0.0493

Gnomad SAS exome

AF:

0.0434

Gnomad FIN exome

AF:

0.0469

Gnomad NFE exome

AF:

0.0700

Gnomad OTH exome

AF:

0.0745

GnomAD4 exome

AF:

0.0662

AC:

96728

AN:

1460862

Hom.:

3364

Cov.:

AF XY:

0.0655

AC XY:

47586

AN XY:

726748

show subpopulations

Gnomad4 AFR exome

AF:

0.0428

Gnomad4 AMR exome

AF:

0.0960

Gnomad4 ASJ exome

AF:

0.0636

Gnomad4 EAS exome

AF:

0.0614

Gnomad4 SAS exome

AF:

0.0434

Gnomad4 FIN exome

AF:

0.0471

Gnomad4 NFE exome

AF:

0.0686

Gnomad4 OTH exome

AF:

0.0626

GnomAD4 genome

AF:

0.0589

AC:

8967

AN:

152206

Hom.:

330

Cov.:

AF XY:

0.0584

AC XY:

4346

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0396

Gnomad4 AMR

AF:

0.0830

Gnomad4 ASJ

AF:

0.0648

Gnomad4 EAS

AF:

0.0492

Gnomad4 SAS

AF:

0.0419

Gnomad4 FIN

AF:

0.0452

Gnomad4 NFE

AF:

0.0688

Gnomad4 OTH

AF:

0.0744

Alfa

AF:

0.0697

Hom.:

867

Bravo

AF:

0.0624

TwinsUK

AF:

0.0696

AC:

258

ALSPAC

AF:

0.0719

AC:

277

ESP6500AA

AF:

0.0388

AC:

157

ESP6500EA

AF:

0.0647

AC:

544

ExAC

AF:

0.0645

AC:

7807

Asia WGS

AF:

0.0530

AC:

186

AN:

3478

EpiCase

AF:

0.0797

EpiControl

AF:

0.0761

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CLTCL1-related disorder

Benign:1

Mar 27, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

0.10

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.14

.;T;T;.

Eigen

Benign

-0.041

Eigen_PC

Benign

-0.065

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

0.97

D;D;D;D

MetaRNN

Benign

0.0033

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;.;.

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.2

.;D;.;.

REVEL

Benign

0.079

Sift

Benign

0.13

.;T;.;.

Sift4G

Benign

0.21

T;T;D;T

Polyphen

0.0030

B;B;.;.

Vest4

0.29

ClinPred

0.025

GERP RS

3.6

Varity_R

0.091

gMVP

0.46

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