Variant 12-7737444-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001371390.1(CLEC4C):c.366C>A(p.Asn122Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,612,962 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 71 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 63 hom. )

Consequence

CLEC4C
NM_001371390.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.43

Variant links:

Genes affected

CLEC4C (HGNC:13258): (C-type lectin domain family 4 member C) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type 2 transmembrane protein may play a role in dendritic cell function. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

CLEC4C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037682354).

BP6

Variant 12-7737444-G-T is Benign according to our data. Variant chr12-7737444-G-T is described in ClinVar as [Benign]. Clinvar id is 768512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC4C	NM_001371390.1 linkuse as main transcript	c.366C>A	p.Asn122Lys	missense_variant	4/6	ENST00000360345.8	NP_001358319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC4C	ENST00000360345.8 linkuse as main transcript	c.366C>A	p.Asn122Lys	missense_variant	4/6	1	NM_001371390.1	ENSP00000353500.3		Q8WTT0-1

Frequencies

GnomAD3 genomes

AF:

0.0161

AC:

2440

AN:

151664

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0564

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00409

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00419

AC:

1052

AN:

250974

Hom.:

AF XY:

0.00304

AC XY:

413

AN XY:

135660

show subpopulations

Gnomad AFR exome

AF:

0.0585

Gnomad AMR exome

AF:

0.00183

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:

0.000220

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00166

AC:

2422

AN:

1461182

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

1037

AN XY:

726886

show subpopulations

Gnomad4 AFR exome

AF:

0.0598

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000962

Gnomad4 OTH exome

AF:

0.00318

GnomAD4 genome

AF:

0.0161

AC:

2441

AN:

151780

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1117

AN XY:

74148

show subpopulations

Gnomad4 AFR

AF:

0.0562

Gnomad4 AMR

AF:

0.00402

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.00677

Hom.:

Bravo

AF:

0.0177

ESP6500AA

AF:

0.0533

AC:

235

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00521

AC:

632

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000437

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.042

T;.;.;T;.;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.85

.;.;T;T;T;D

MetaRNN

Benign

0.0038

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.;.;L;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.6

D;D;D;D;D;D

REVEL

Benign

0.086

Sift

Benign

0.040

D;D;D;D;D;D

Sift4G

Uncertain

0.030

D;D;D;D;D;D

Polyphen

0.94

P;P;P;P;.;.

Vest4

0.33

MutPred

0.55

Gain of ubiquitination at N122 (P = 0.0276);.;.;Gain of ubiquitination at N122 (P = 0.0276);.;.;

MVP

0.57

MPC

0.94

ClinPred

0.053

GERP RS

2.6

Varity_R

0.34

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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