Variant rs1862511 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
CD70	NM_001252.5 linkuse as main transcript	c.345C>T	p.Cys115Cys	synonymous_variant	3/3	ENST00000245903.4	NP_001243.1	P32970-1A0A0U5JA32
CD70	NM_001330332.2 linkuse as main transcript	c.345C>T	p.Cys115Cys	synonymous_variant	3/4		NP_001317261.1	P32970-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD70	ENST00000245903.4 linkuse as main transcript	c.345C>T	p.Cys115Cys	synonymous_variant	3/3	1	NM_001252.5	ENSP00000245903.2		P32970-1
CD70	ENST00000423145.7 linkuse as main transcript	c.345C>T	p.Cys115Cys	synonymous_variant	3/4	2		ENSP00000395294.2		P32970-2

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

GnomAD3 exomes

AF:

0.319

AC:

80052

AN:

251254

Hom.:

14777

AF XY:

0.323

AC XY:

43855

AN XY:

135814

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 SAS exome

AF:

0.338

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

Gnomad4 AFR exome

AF:

0.192

Gnomad4 AMR exome

AF:

0.219

Gnomad4 ASJ exome

AF:

0.251

Gnomad4 EAS exome

AF:

0.686

Gnomad4 SAS exome

AF:

0.340

Gnomad4 FIN exome

AF:

0.380

Gnomad4 NFE exome

AF:

0.290

Gnomad4 OTH exome

AF:

0.309

GnomAD4 genome

AF:

0.281

AC:

42672

AN:

152026

Hom.:

6608

Cov.:

AF XY:

0.288

AC XY:

21377

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.199

Gnomad4 AMR

AF:

0.251

Gnomad4 ASJ

AF:

0.252

Gnomad4 EAS

AF:

0.685

Gnomad4 SAS

AF:

0.356

Gnomad4 FIN

AF:

0.388

Gnomad4 NFE

AF:

0.285

Gnomad4 OTH

AF:

0.296

Alfa

AF:

0.287

Hom.:

12846

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

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

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

DANN

Benign

0.65

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