rs10489990

Variant summary

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

The NM_015717.5(CD207):​c.164C>T​(p.Ala55Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,612,328 control chromosomes in the GnomAD database, including 96,343 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict 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 0.30 ( 7379 hom., cov: 32)
Exomes 𝑓: 0.35 ( 88964 hom. )

Consequence

CD207
NM_015717.5 missense

Scores

4
14

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.88
Variant links:
Genes affected
CD207 (HGNC:17935): (CD207 molecule) The protein encoded by this gene is expressed only in Langerhans cells which are immature dendritic cells of the epidermis and mucosa. It is localized in the Birbeck granules, organelles present in the cytoplasm of Langerhans cells and consisting of superimposed and zippered membranes. It is a C-type lectin with mannose binding specificity, and it has been proposed that mannose binding by this protein leads to internalization of antigen into Birbeck granules and providing access to a nonclassical antigen-processing pathway. Mutations in this gene result in Birbeck granules deficiency or loss of sugar binding activity. [provided by RefSeq, Aug 2010]

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=0.004815489).
BP6
Variant 2-70835517-G-A is Benign according to our data. Variant chr2-70835517-G-A is described in ClinVar as [Benign]. Clinvar id is 3059383.Status of the report is no_assertion_criteria_provided, 0 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CD207NM_015717.5 linkc.164C>T p.Ala55Val missense_variant 2/6 ENST00000410009.5 NP_056532.4 Q9UJ71
CD207XM_011532875.3 linkc.164C>T p.Ala55Val missense_variant 2/7 XP_011531177.1
CD207XM_011532876.3 linkc.164C>T p.Ala55Val missense_variant 2/6 XP_011531178.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CD207ENST00000410009.5 linkc.164C>T p.Ala55Val missense_variant 2/61 NM_015717.5 ENSP00000386378.3 Q9UJ71

Frequencies

GnomAD3 genomes
AF:
0.298
AC:
45249
AN:
151978
Hom.:
7371
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.156
Gnomad AMI
AF:
0.349
Gnomad AMR
AF:
0.361
Gnomad ASJ
AF:
0.382
Gnomad EAS
AF:
0.299
Gnomad SAS
AF:
0.294
Gnomad FIN
AF:
0.327
Gnomad MID
AF:
0.418
Gnomad NFE
AF:
0.359
Gnomad OTH
AF:
0.320
GnomAD3 exomes
AF:
0.333
AC:
82843
AN:
248744
Hom.:
14335
AF XY:
0.334
AC XY:
45008
AN XY:
134944
show subpopulations
Gnomad AFR exome
AF:
0.149
Gnomad AMR exome
AF:
0.400
Gnomad ASJ exome
AF:
0.374
Gnomad EAS exome
AF:
0.278
Gnomad SAS exome
AF:
0.291
Gnomad FIN exome
AF:
0.330
Gnomad NFE exome
AF:
0.354
Gnomad OTH exome
AF:
0.346
GnomAD4 exome
AF:
0.346
AC:
504847
AN:
1460232
Hom.:
88964
Cov.:
35
AF XY:
0.344
AC XY:
250108
AN XY:
726450
show subpopulations
Gnomad4 AFR exome
AF:
0.155
Gnomad4 AMR exome
AF:
0.397
Gnomad4 ASJ exome
AF:
0.380
Gnomad4 EAS exome
AF:
0.309
Gnomad4 SAS exome
AF:
0.286
Gnomad4 FIN exome
AF:
0.335
Gnomad4 NFE exome
AF:
0.356
Gnomad4 OTH exome
AF:
0.334
GnomAD4 genome
AF:
0.298
AC:
45269
AN:
152096
Hom.:
7379
Cov.:
32
AF XY:
0.297
AC XY:
22085
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.155
Gnomad4 AMR
AF:
0.360
Gnomad4 ASJ
AF:
0.382
Gnomad4 EAS
AF:
0.299
Gnomad4 SAS
AF:
0.295
Gnomad4 FIN
AF:
0.327
Gnomad4 NFE
AF:
0.359
Gnomad4 OTH
AF:
0.325
Alfa
AF:
0.345
Hom.:
20526
Bravo
AF:
0.294
TwinsUK
AF:
0.356
AC:
1319
ALSPAC
AF:
0.338
AC:
1303
ESP6500AA
AF:
0.152
AC:
640
ESP6500EA
AF:
0.349
AC:
2952
ExAC
AF:
0.328
AC:
39688
Asia WGS
AF:
0.303
AC:
1060
AN:
3478
EpiCase
AF:
0.358
EpiControl
AF:
0.356

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

CD207-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesOct 18, 2019This 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
0.096
BayesDel_addAF
Benign
-0.75
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T
Eigen
Benign
-0.73
Eigen_PC
Benign
-0.69
FATHMM_MKL
Benign
0.43
N
LIST_S2
Benign
0.75
T
MetaRNN
Benign
0.0048
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.037
Sift
Uncertain
0.029
D
Sift4G
Uncertain
0.011
D
Polyphen
0.27
B
Vest4
0.038
MPC
0.49
ClinPred
0.0091
T
GERP RS
4.0
Varity_R
0.042
gMVP
0.28

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: rs10489990; hg19: chr2-71062648; COSMIC: COSV69651801; API