dbSNP rs1862511: CD70:p.Cys115Cys (chr19-6586257-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001252.5(CD70):c.345C>T(p.Cys115Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,613,640 control chromosomes in the GnomAD database, including 77,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.28 ( 6608 hom., cov: 31)

Exomes 𝑓: 0.30 ( 71098 hom. )

Consequence

CD70
NM_001252.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.21

Publications

16 publications found

Variant links:

Genes affected

CD70 (HGNC:11937): (CD70 molecule) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for TNFRSF27/CD27. It is a surface antigen on activated, but not on resting, T and B lymphocytes. It induces proliferation of costimulated T cells, enhances the generation of cytolytic T cells, and contributes to T cell activation. This cytokine is also reported to play a role in regulating B-cell activation, cytotoxic function of natural killer cells, and immunoglobulin sythesis. [provided by RefSeq, Jul 2008]

CD70 Gene-Disease associations (from GenCC):

severe combined immunodeficiency due to CD70 deficiency
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

CD70 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 19-6586257-G-A is Benign according to our data. Variant chr19-6586257-G-A is described in ClinVar as Benign. ClinVar VariationId is 2628186.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.21 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD70	NM_001252.5 link	c.345C>T	p.Cys115Cys	synonymous_variant	Exon 3 of 3	ENST00000245903.4	NP_001243.1
CD70	NM_001330332.2 link	c.345C>T	p.Cys115Cys	synonymous_variant	Exon 3 of 4		NP_001317261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD70	ENST00000245903.4 link	c.345C>T	p.Cys115Cys	synonymous_variant	Exon 3 of 3	1	NM_001252.5	ENSP00000245903.2
CD70	ENST00000423145.7 link	c.345C>T	p.Cys115Cys	synonymous_variant	Exon 3 of 4	2		ENSP00000395294.2

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42669

AN:

151908

Hom.:

6611

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.341

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.252

Gnomad EAS

AF:

0.686

Gnomad SAS

AF:

0.356

Gnomad FIN

AF:

0.388

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.294

GnomAD2 exomes

AF:

0.319

AC:

80052

AN:

251254

AF XY:

0.323

show subpopulations

Gnomad AFR exome

AF:

0.202

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.256

Gnomad EAS exome

AF:

0.695

Gnomad FIN exome

AF:

0.381

Gnomad NFE exome

AF:

0.297

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.302

AC:

441946

AN:

1461614

Hom.:

71098

Cov.:

AF XY:

0.304

AC XY:

220865

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.192

AC:

6421

AN:

33470

American (AMR)

AF:

0.219

AC:

9798

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

6552

AN:

26134

East Asian (EAS)

AF:

0.686

AC:

27239

AN:

39698

South Asian (SAS)

AF:

0.340

AC:

29329

AN:

86248

European-Finnish (FIN)

AF:

0.380

AC:

20286

AN:

53386

Middle Eastern (MID)

AF:

0.270

AC:

1530

AN:

5664

European-Non Finnish (NFE)

AF:

0.290

AC:

322137

AN:

1111918

Other (OTH)

AF:

0.309

AC:

18654

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

18528

37056

55583

74111

92639

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10848

21696

32544

43392

54240

<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:

0.281

AC:

42672

AN:

152026

Hom.:

6608

Cov.:

AF XY:

0.288

AC XY:

21377

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.199

AC:

8235

AN:

41478

American (AMR)

AF:

0.251

AC:

3842

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

874

AN:

3470

East Asian (EAS)

AF:

0.685

AC:

3517

AN:

5134

South Asian (SAS)

AF:

0.356

AC:

1720

AN:

4828

European-Finnish (FIN)

AF:

0.388

AC:

4103

AN:

10572

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.285

AC:

19374

AN:

67952

Other (OTH)

AF:

0.296

AC:

625

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1519

3038

4558

6077

7596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.287

Hom.:

27187

Bravo

AF:

0.272

Asia WGS

AF:

0.477

AC:

1656

AN:

3478

EpiCase

AF:

0.293

EpiControl

AF:

0.298

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 48% of patients studied by a panel of primary immunodeficiencies. Number of patients: 46. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.0

(source)

DANN

Benign

0.65

PhyloP100

1.2

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over