Genetic Variant NM_015717.5:c.164C>T (chr2-70835517-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A55T) has been classified as Uncertain significance.

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

Publications

32 publications found

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 Gene-Disease associations (from GenCC):

Birbeck granule deficiency
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

CD207 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015717.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD207	NM_015717.5	MANE Select	c.164C>T	p.Ala55Val	missense	Exon 2 of 6	NP_056532.4	Q9UJ71

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD207	ENST00000410009.5	TSL:1 MANE Select	c.164C>T	p.Ala55Val	missense	Exon 2 of 6	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

GnomAD2 exomes

AF:

0.333

AC:

82843

AN:

248744

AF XY:

0.334

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 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

African (AFR)

AF:

0.155

AC:

5178

AN:

33468

American (AMR)

AF:

0.397

AC:

17750

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.380

AC:

9932

AN:

26130

East Asian (EAS)

AF:

0.309

AC:

12269

AN:

39680

South Asian (SAS)

AF:

0.286

AC:

24674

AN:

86222

European-Finnish (FIN)

AF:

0.335

AC:

17859

AN:

53378

Middle Eastern (MID)

AF:

0.353

AC:

1981

AN:

5604

European-Non Finnish (NFE)

AF:

0.356

AC:

395055

AN:

1110760

Other (OTH)

AF:

0.334

AC:

20149

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

17110

34220

51330

68440

85550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12498

24996

37494

49992

62490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.298

AC:

45269

AN:

152096

Hom.:

7379

Cov.:

AF XY:

0.297

AC XY:

22085

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.155

AC:

6447

AN:

41502

American (AMR)

AF:

0.360

AC:

5506

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

1327

AN:

3472

East Asian (EAS)

AF:

0.299

AC:

1543

AN:

5160

South Asian (SAS)

AF:

0.295

AC:

1419

AN:

4810

European-Finnish (FIN)

AF:

0.327

AC:

3460

AN:

10568

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.359

AC:

24437

AN:

67992

Other (OTH)

AF:

0.325

AC:

687

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1596

3193

4789

6386

7982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.340

Hom.:

39803

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

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

CD207-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

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

PhyloP100

1.9

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

PromoterAI

0.0084

Neutral

(source)

Varity_R

0.042

gMVP

0.28

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over