Variant rs200837270 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_015717.5(CD207):c.790T>C(p.Trp264Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00335 in 1,613,744 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 10 hom. )

Consequence

CD207
NM_015717.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:2

Conservation

PhyloP100: 4.37

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]

CD207 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 273 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CD207	NM_015717.5 linkuse as main transcript	c.790T>C	p.Trp264Arg	missense_variant	5/6	ENST00000410009.5	NP_056532.4
CD207	XM_011532875.3 linkuse as main transcript	c.790T>C	p.Trp264Arg	missense_variant	5/7		XP_011531177.1
CD207	XM_011532876.3 linkuse as main transcript	c.790T>C	p.Trp264Arg	missense_variant	5/6		XP_011531178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD207	ENST00000410009.5 linkuse as main transcript	c.790T>C	p.Trp264Arg	missense_variant	5/6	1	NM_015717.5	ENSP00000386378	P1

Frequencies

GnomAD3 genomes

AF:

0.00179

AC:

272

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00310

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00212

AC:

528

AN:

249258

Hom.:

AF XY:

0.00210

AC XY:

284

AN XY:

135222

show subpopulations

Gnomad AFR exome

AF:

0.000646

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000784

Gnomad FIN exome

AF:

0.000510

Gnomad NFE exome

AF:

0.00352

Gnomad OTH exome

AF:

0.00347

GnomAD4 exome

AF:

0.00351

AC:

5128

AN:

1461438

Hom.:

Cov.:

AF XY:

0.00343

AC XY:

2495

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00272

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000858

Gnomad4 FIN exome

AF:

0.000581

Gnomad4 NFE exome

AF:

0.00426

Gnomad4 OTH exome

AF:

0.00234

GnomAD4 genome

AF:

0.00179

AC:

273

AN:

152306

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

125

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.00312

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00345

Hom.:

Bravo

AF:

0.00188

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.00123

AC:

ESP6500EA

AF:

0.00347

AC:

ExAC

AF:

0.00219

AC:

265

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00245

EpiControl

AF:

0.00397

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Birbeck granule deficiency

Pathogenic:1Uncertain:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Jun 02, 2006	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	Apr 04, 2024	- -

not provided

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Uncertain

0.10

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Uncertain

0.45

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.59

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.47

MetaSVM

Uncertain

-0.19

MutationAssessor

Pathogenic

3.8

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-13

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.97

MutPred

0.96

Gain of disorder (P = 0.0087);

MVP

0.57

MPC

0.84

ClinPred

0.14

GERP RS

4.5

Varity_R

0.95

gMVP

0.93

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