22-19180775-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_007098.4(CLTCL1):​c.4859G>A​(p.Arg1620His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00929 in 1,613,786 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0072 ( 17 hom., cov: 34)
Exomes 𝑓: 0.0095 ( 175 hom. )

Consequence

CLTCL1
NM_007098.4 missense

Scores

2
16

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.293
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0017917454).
BP6
Variant 22-19180775-C-T is Benign according to our data. Variant chr22-19180775-C-T is described in ClinVar as [Benign]. Clinvar id is 2652855.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00722 (1099/152316) while in subpopulation SAS AF= 0.0495 (239/4826). AF 95% confidence interval is 0.0444. There are 17 homozygotes in gnomad4. There are 573 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 17 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLTCL1NM_007098.4 linkc.4859G>A p.Arg1620His missense_variant Exon 31 of 33 ENST00000427926.6 NP_009029.3 P53675-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLTCL1ENST00000427926.6 linkc.4859G>A p.Arg1620His missense_variant Exon 31 of 33 1 NM_007098.4 ENSP00000441158.1 P53675-1

Frequencies

GnomAD3 genomes
AF:
0.00725
AC:
1103
AN:
152198
Hom.:
17
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00157
Gnomad AMI
AF:
0.0285
Gnomad AMR
AF:
0.00739
Gnomad ASJ
AF:
0.0187
Gnomad EAS
AF:
0.0106
Gnomad SAS
AF:
0.0501
Gnomad FIN
AF:
0.000377
Gnomad MID
AF:
0.0316
Gnomad NFE
AF:
0.00742
Gnomad OTH
AF:
0.00860
GnomAD3 exomes
AF:
0.0119
AC:
2961
AN:
249178
Hom.:
59
AF XY:
0.0140
AC XY:
1893
AN XY:
135204
show subpopulations
Gnomad AFR exome
AF:
0.00149
Gnomad AMR exome
AF:
0.00574
Gnomad ASJ exome
AF:
0.0207
Gnomad EAS exome
AF:
0.0103
Gnomad SAS exome
AF:
0.0472
Gnomad FIN exome
AF:
0.000836
Gnomad NFE exome
AF:
0.00712
Gnomad OTH exome
AF:
0.0135
GnomAD4 exome
AF:
0.00950
AC:
13886
AN:
1461470
Hom.:
175
Cov.:
31
AF XY:
0.0107
AC XY:
7747
AN XY:
727030
show subpopulations
Gnomad4 AFR exome
AF:
0.00128
Gnomad4 AMR exome
AF:
0.00635
Gnomad4 ASJ exome
AF:
0.0203
Gnomad4 EAS exome
AF:
0.00668
Gnomad4 SAS exome
AF:
0.0458
Gnomad4 FIN exome
AF:
0.000826
Gnomad4 NFE exome
AF:
0.00717
Gnomad4 OTH exome
AF:
0.0106
GnomAD4 genome
AF:
0.00722
AC:
1099
AN:
152316
Hom.:
17
Cov.:
34
AF XY:
0.00769
AC XY:
573
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.00156
Gnomad4 AMR
AF:
0.00738
Gnomad4 ASJ
AF:
0.0187
Gnomad4 EAS
AF:
0.0106
Gnomad4 SAS
AF:
0.0495
Gnomad4 FIN
AF:
0.000377
Gnomad4 NFE
AF:
0.00742
Gnomad4 OTH
AF:
0.00899
Alfa
AF:
0.00813
Hom.:
7
Bravo
AF:
0.00652
TwinsUK
AF:
0.00674
AC:
25
ALSPAC
AF:
0.00830
AC:
32
ESP6500AA
AF:
0.000703
AC:
3
ESP6500EA
AF:
0.00787
AC:
67
ExAC
AF:
0.0120
AC:
1453
Asia WGS
AF:
0.0310
AC:
106
AN:
3478
EpiCase
AF:
0.00878
EpiControl
AF:
0.00883

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jul 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

CLTCL1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.064
BayesDel_addAF
Benign
-0.58
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
0.22
DANN
Benign
0.90
DEOGEN2
Benign
0.21
.;T;T;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.14
N
LIST_S2
Uncertain
0.86
D;D;D;D
MetaRNN
Benign
0.0018
T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.8
.;L;.;.
PrimateAI
Benign
0.18
T
PROVEAN
Benign
-2.0
.;N;.;.
REVEL
Benign
0.16
Sift
Benign
0.054
.;T;.;.
Sift4G
Uncertain
0.056
T;T;T;T
Polyphen
0.016
B;B;.;.
Vest4
0.099
ClinPred
0.014
T
GERP RS
-5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.028
gMVP
0.47

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.

Other links and lift over

dbSNP: rs5748024; hg19: chr22-19168288; COSMIC: COSV53206853; COSMIC: COSV53206853; API