rs2024301

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016184.4(CLEC4A):​c.107A>T​(p.His36Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 1,608,236 control chromosomes in the GnomAD database, including 337,036 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.57 ( 25746 hom., cov: 31)
Exomes 𝑓: 0.65 ( 311290 hom. )

Consequence

CLEC4A
NM_016184.4 missense

Scores

2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.170
Variant links:
Genes affected
CLEC4A (HGNC:13257): (C-type lectin domain family 4 member A) 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 inflammatory and immune response. Multiple transcript variants encoding distinct isoforms have been identified for this gene. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=1.0386118E-5).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CLEC4ANM_016184.4 linkuse as main transcriptc.107A>T p.His36Leu missense_variant 2/6 ENST00000229332.12 NP_057268.1 Q9UMR7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CLEC4AENST00000229332.12 linkuse as main transcriptc.107A>T p.His36Leu missense_variant 2/61 NM_016184.4 ENSP00000229332.5 Q9UMR7-1

Frequencies

GnomAD3 genomes
AF:
0.568
AC:
86302
AN:
151878
Hom.:
25737
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.390
Gnomad AMI
AF:
0.630
Gnomad AMR
AF:
0.535
Gnomad ASJ
AF:
0.664
Gnomad EAS
AF:
0.528
Gnomad SAS
AF:
0.523
Gnomad FIN
AF:
0.619
Gnomad MID
AF:
0.642
Gnomad NFE
AF:
0.675
Gnomad OTH
AF:
0.616
GnomAD3 exomes
AF:
0.592
AC:
148661
AN:
251092
Hom.:
45394
AF XY:
0.599
AC XY:
81244
AN XY:
135714
show subpopulations
Gnomad AFR exome
AF:
0.385
Gnomad AMR exome
AF:
0.456
Gnomad ASJ exome
AF:
0.647
Gnomad EAS exome
AF:
0.530
Gnomad SAS exome
AF:
0.515
Gnomad FIN exome
AF:
0.631
Gnomad NFE exome
AF:
0.678
Gnomad OTH exome
AF:
0.646
GnomAD4 exome
AF:
0.649
AC:
945497
AN:
1456240
Hom.:
311290
Cov.:
33
AF XY:
0.646
AC XY:
468426
AN XY:
724728
show subpopulations
Gnomad4 AFR exome
AF:
0.390
Gnomad4 AMR exome
AF:
0.470
Gnomad4 ASJ exome
AF:
0.649
Gnomad4 EAS exome
AF:
0.561
Gnomad4 SAS exome
AF:
0.525
Gnomad4 FIN exome
AF:
0.636
Gnomad4 NFE exome
AF:
0.679
Gnomad4 OTH exome
AF:
0.631
GnomAD4 genome
AF:
0.568
AC:
86361
AN:
151996
Hom.:
25746
Cov.:
31
AF XY:
0.565
AC XY:
41925
AN XY:
74264
show subpopulations
Gnomad4 AFR
AF:
0.390
Gnomad4 AMR
AF:
0.535
Gnomad4 ASJ
AF:
0.664
Gnomad4 EAS
AF:
0.529
Gnomad4 SAS
AF:
0.525
Gnomad4 FIN
AF:
0.619
Gnomad4 NFE
AF:
0.675
Gnomad4 OTH
AF:
0.611
Alfa
AF:
0.646
Hom.:
10443
Bravo
AF:
0.554
TwinsUK
AF:
0.682
AC:
2530
ALSPAC
AF:
0.693
AC:
2669
ESP6500AA
AF:
0.404
AC:
1778
ESP6500EA
AF:
0.674
AC:
5797
ExAC
AF:
0.597
AC:
72467
Asia WGS
AF:
0.506
AC:
1761
AN:
3478
EpiCase
AF:
0.668
EpiControl
AF:
0.673

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
9.3
DANN
Benign
0.48
DEOGEN2
Benign
0.057
T;.;.
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.013
N
LIST_S2
Benign
0.30
T;T;T
MetaRNN
Benign
0.000010
T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.7
L;L;.
PrimateAI
Benign
0.33
T
PROVEAN
Uncertain
-3.6
D;D;.
REVEL
Benign
0.081
Sift
Benign
0.067
T;T;.
Sift4G
Uncertain
0.017
D;D;.
Polyphen
0.96
D;D;.
Vest4
0.18
MPC
0.26
ClinPred
0.052
T
GERP RS
-1.3
Varity_R
0.12
gMVP
0.42

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: rs2024301; hg19: chr12-8278181; COSMIC: COSV57561481; COSMIC: COSV57561481; API