Variant chr12-9722722-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000327839.4(CLECL1P):n.443G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CLECL1P
ENST00000327839.4 non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0230

Variant links:

Genes affected

CLECL1P (HGNC:24462): (C-type lectin like 1, pseudogene) This gene encodes a type II transmembrane, C-type lectin-like protein that is highly expressed on dendritic and B cells. This protein may act as a T-cell costimulatory molecule that enhances interleukin-4 production, and maybe involved in the regulation of the immune response. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

CLECL1P links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.121448904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLECL1P	NR_172485.1 link	n.440G>C		non_coding_transcript_exon_variant	2/3
CLECL1P	NR_172486.1 link	n.440G>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL
CLECL1P	ENST00000327839.4 link	n.443G>C	non_coding_transcript_exon_variant	2/2	1
CLECL1P	ENST00000542530.5 link	n.263G>C	non_coding_transcript_exon_variant	2/3	4
CLECL1P	ENST00000621400.5 link	n.354G>C	non_coding_transcript_exon_variant	4/4	5
CLECL1P	ENST00000702603.1 link	n.241G>C	non_coding_transcript_exon_variant	2/3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251298

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461654

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

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

Ambry Genetics

Oct 12, 2021

The c.408G>C (p.K136N) alteration is located in exon 2 (coding exon 2) of the CLECL1 gene. This alteration results from a G to C substitution at nucleotide position 408, causing the lysine (K) at amino acid position 136 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.64

CADD

Benign

3.2

DANN

Benign

0.96

DEOGEN2

Benign

0.019

.;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.38

T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.0

.;M

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.2

.;N

REVEL

Benign

0.030

Sift

Benign

0.069

.;T

Sift4G

Uncertain

0.025

D;D

Polyphen

0.99

.;D

Vest4

0.14

MutPred

0.45

Loss of methylation at K136 (P = 0.0176);Loss of methylation at K136 (P = 0.0176);

MVP

0.085

MPC

0.27

ClinPred

0.059

GERP RS

-0.061

Varity_R

0.15

gMVP

0.34

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