Variant rs10489990 details in Genebe, Genetics Data Aggregator

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

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]

CD207 links:

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
CD207	NM_015717.5 link	c.164C>T	p.Ala55Val	missense_variant	2/6	ENST00000410009.5	NP_056532.4	Q9UJ71
CD207	XM_011532875.3 link	c.164C>T	p.Ala55Val	missense_variant	2/7		XP_011531177.1
CD207	XM_011532876.3 link	c.164C>T	p.Ala55Val	missense_variant	2/6		XP_011531178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD207	ENST00000410009.5 link	c.164C>T	p.Ala55Val	missense_variant	2/6	1	NM_015717.5	ENSP00000386378.3		Q9UJ71

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45249

AN:

151978

Hom.:

7371

Cov.:

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.:

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.:

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 provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This 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

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0048

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.3

REVEL

Benign

0.037

Sift

Uncertain

0.029

Sift4G

Uncertain

0.011

Polyphen

0.27

Vest4

0.038

MPC

0.49

ClinPred

0.0091

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.

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