Genetic Variant CD70:c.197-82A>G (chr19-6586487-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001252.5(CD70):c.197-82A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 1,394,454 control chromosomes in the GnomAD database, including 6,766 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.094 ( 712 hom., cov: 30)

Exomes 𝑓: 0.097 ( 6054 hom. )

Consequence

CD70
NM_001252.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.88

Publications

10 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD70	NM_001252.5 link	c.197-82A>G		intron_variant	Intron 2 of 2	ENST00000245903.4	NP_001243.1
CD70	NM_001330332.2 link	c.197-82A>G		intron_variant	Intron 2 of 3		NP_001317261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD70	ENST00000245903.4 link	c.197-82A>G		intron_variant	Intron 2 of 2	1	NM_001252.5	ENSP00000245903.2
CD70	ENST00000423145.7 link	c.197-82A>G		intron_variant	Intron 2 of 3	2		ENSP00000395294.2

Frequencies

GnomAD3 genomes

AF:

0.0937

AC:

14217

AN:

151716

Hom.:

714

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0901

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0752

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.0392

Gnomad SAS

AF:

0.0733

Gnomad FIN

AF:

0.0934

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.102

GnomAD4 exome

AF:

0.0971

AC:

120665

AN:

1242620

Hom.:

6054

AF XY:

0.0976

AC XY:

59779

AN XY:

612476

show subpopulations

African (AFR)

AF:

0.0925

AC:

2620

AN:

28338

American (AMR)

AF:

0.0625

AC:

1738

AN:

27806

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

2155

AN:

19436

East Asian (EAS)

AF:

0.0399

AC:

1497

AN:

37474

South Asian (SAS)

AF:

0.0849

AC:

5688

AN:

66966

European-Finnish (FIN)

AF:

0.0975

AC:

3528

AN:

36200

Middle Eastern (MID)

AF:

0.126

AC:

449

AN:

3566

European-Non Finnish (NFE)

AF:

0.101

AC:

97746

AN:

970372

Other (OTH)

AF:

0.100

AC:

5244

AN:

52462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

5472

10945

16417

21890

27362

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3558

7116

10674

14232

17790

<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:

0.0937

AC:

14229

AN:

151834

Hom.:

712

Cov.:

AF XY:

0.0920

AC XY:

6826

AN XY:

74198

show subpopulations

African (AFR)

AF:

0.0902

AC:

3732

AN:

41370

American (AMR)

AF:

0.0751

AC:

1145

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

385

AN:

3470

East Asian (EAS)

AF:

0.0391

AC:

202

AN:

5172

South Asian (SAS)

AF:

0.0732

AC:

352

AN:

4812

European-Finnish (FIN)

AF:

0.0934

AC:

986

AN:

10552

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.105

AC:

7126

AN:

67902

Other (OTH)

AF:

0.103

AC:

216

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

661

1321

1982

2642

3303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<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:

0.0993

Hom.:

1391

Bravo

AF:

0.0916

Asia WGS

AF:

0.0770

AC:

268

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.34

(source)

DANN

Benign

0.45

PhyloP100

-1.9

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over